Trots 2013

Leiden Science Waar wij trots op zijn Our Talents & Discoveries OF 2013

de ontdekkingen van 2012

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Faculty of Science Faculteit der Wiskunde & Natuurwetenschappen

Colofon Leiden Science, Our Talents and Discoveries of 2013.

Editorial team Geert de Snoo, Ron van Veen, Marjolein van Schoonhoven Contributing writers Nienke Beintema, Willy van Strien, Anouck Vrouwe, Bruno van Wayenburg, Marcus Werner, Marjolein van Schoonhoven Photography Pim Rusch, Philip Mynott (photo Gerard van Westen) Florian Maucher (photo Sandra Scanu) Beeldbank Leiden University English translation Wilkens C.S., Marcus Werner Design www.balyon.com Printed by De Bink Leiden Contact Faculty of Science, Leiden University Marketing and Communications P.O. Box 9502 2300 RA Leiden The Netherlands voorlichting@science.leidenuniv.nl All rights reserved: Faculty of Science, Leiden U ­ niversity.

Privacy and publicity rights apply. Reproduction of (parts of) this publication is only prohibited after written permission from the publisher. Enquiries can be sent to: voorlichting@science.leidenuniv.nl

Content

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Facts & Figures

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Foreword Dean

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C.J. Kok Awards and Faculty Award for Education C.J. Kok Public Award Awards and Prices in 2013 research

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C.J. Kok Jury Award

Faculty Award for Education Awards and Prices in 2013 education Science Campus

Our science community

Facts & Figures Institutes

Institute of Biology Leiden Institute of Environmental Sciences Leiden Academic Centre for Drug Research Leiden Institute of Advanced Computer Science Leiden Institute of Chemistry Leiden Institute of Physics Leiden Observatory Mathematical Institute

(National) Facilities

Cell Observatory Hortus botanicus Leiden Lorentz Center Metabolomics Center NeCen Paramagnetic NMR facility

Total turnover 100 ME

Research profile areas

Scientific staff

Graduate School of Science (MSc programmes and PhD)

BSc programmes -1605 students

MSc programmes - 1050 students

Fundamentals of Science Bioscience: the science base of health Translational drug discovery and development

Astronomy Bio-Pharmaceutical Sciences Biology Computer Science

(including Computer Science and Economy)

Life Science and Technology

(joint programme with Delft University of Technology)

Molecular Science and Technology

(joint programme with Delft University of Technology)

Mathematics Physics

122 full professors 114 associate and assistant professors 165 Post doc’s 640 PhD’s (including guests)

Astronomy Life Science and Technology Bio-Pharmaceutical Sciences Mathematics Biology Media Technology Chemistry Physics Computer Science (including Bioinformatics) ICT in Business Industrial Ecology (joint programme with Delft University of Technology) If appropriate with MSc specialisations: Science Based Business, Science Communication and Society Education

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Foreword Dean

The Faculty of Science; Science for Impact !

At the Faculty of Science of Leiden University we are aiming to excel in both research and education in a broad range of disciplines. In each of our institutes, mathematics, computer science, astronomy, physics, chemistry, bio-pharmaceutical sciences, biology and environmental sciences, the leading criteria in building a strong research and education portfolio are scientific impact, technological innovation and societal relevance.

To enhance our impact and visibility the Faculty of Science has organized most of its activities around two large and recognisable profile areas: ‘Fundamentals of science’ and ‘Bioscience: the science base of health’. These areas offer new opportunities for fundamental research across the boundaries of our disciplines and connect with important societal challenges. We are attracting top talent to Leiden from The Netherlands and abroad with our excellent research environment and high-tech facilities. This year, more than 120 of our PhD students successfully defended their thesis. We consider the start of the construction of the new Science campus (February 2013) a milestone in the further development of the Faculty.

In recent years the number of BSc and MSc students enrolled within our Faculty has grown rapidly. We anticipate the number of international master students and PhD students in the Faculty wide Graduate School of Science to increase further.

Teachers, tutors and students are intensely working together in our education programmes that are characterised by a

strong interrelationship between research and education. We aim to challenge talented students, to inspire and amaze them and to educate them to become the successful scientists of tomorrow, who will be able to make important contributions to science and technology, and to a better global environment and society.

We are proud of our science community, staff and students, and of their achievements and of the distinctions and awards that they have obtained in the past year.

The Board of the Faculty of Science, Geert de Snoo

Han de Winde

Gert Jan van Helden

Rembrandt Donkersloot

C.J. Kok Awards and Faculty Award for Education 2013

C.J. Kok Fund

The C.J. Kok fund was formed from the assets of Mr C.J. Kok, biology tutor from The Hague, who was highly committed to the natural sciences. On his death in 1965 he left his entire estate to Leiden University. The C.J. Kok fund was established with this inheritance.

In his will Mr Kok determined that annually both the Faculty of Science and the Leiden University Medical Center would be given the opportunity to use the fund’s revenues to award outstanding performance to those demonstrating ‘a pronounced, significant talent for mathematics or solving medical problems’. The will also stated that the assessment of performance should be on pure scientific grounds and that no distinction should be made regarding ‘rank, status, race, national character, origin, relationship and so on’.

C.J. Kok Awards

The Faculty of Science grants two C.J. Kok awards annually: the C.J. Kok Public Award, also known as the award for the “Discoverer of the Year” and the C.J. Kok Jury Award, the award for the best PhD thesis from the past year. All institutes within the Faculty are given the opportunity to nominate candidates for both awards.

Education Award

Education and Research are closely interrelated in our Faculty. Mono-disciplinary education and multi-disciplinary cooperation give our students the competences they need to become the scientists of tomorrow. Excellent education is of inestimable value in this. Being able to translate research findings successfully into high-quality educational programmes at the Bachelor and Master level is of great importance to stimulate and enthuse students for science and developing a new generation of successful and motivated (natural) scientists.

For this reason, in addition to the C.J. Kok Award, the Faculty also grants the annual Award for Education, a student initiative. Students from the education committees nominate tutors for this award. In a short presentation, they justify their nomination to the jury. The jury, comprising the chairpersons of the study associations and the assessor from the faculty board, subsequently assess each nominated tutor. Most of time it’s a close call between two or more tutors, in that case the jury visits one or more lectures to decide who will be granted the award.

Both C.J. Kok Awards and the Faculty Award for Education are presented at the Faculty’s annual New Year’s reception.

C.J. Kok Public Award Nominees ‘Discoverer of the year 2013’

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Nienke van der Marel Leiden Observatory

Diego Garlaschelli Leiden Institute of Physics

Marco Streng Mathematical Institute

Fons Verbeek Leiden Institute of Advanced Computer Science

Sandra Scanu Leiden Institute of Chemistry

Gerard van Westen Leiden Academic Centre for Drug Research

Maurijn van der Zee en Chris Jacobs Institute of Biology Leiden

Laura Bertola Institute of Environmental ­Sciences

Nienke van der Marel Leiden Observatory

Asymmetric dust tra “Our first response was: ‘What the heck is this?’,” says Nienke van der Marel, a PhD student at the Sterrewacht astronomical institute in Leiden.

When she and her colleagues analysed telescope images of a disk of dust and gas around a star, a puzzling asymmetry showed up. “We really had no clue as to what we were looking at,” Van der Marel says.

By Bruno van Wayenburg The asymmetry turned out to be an accumulation of dust on one side of the star, an ‘asymmetric dust trap’. It’a phenomenon important for the formation of planets from discs of dust and gas around stars, so called ‘transition discs’. The unexpected discovery resulted in a Science publication for Van der Marel and eleven co-authors.

Nienke van der Marel (1986) studied Astronomy

and Instrumentation in Leiden. She became a PhD student in 2011, working with astronomer Ewine van Dishoeck on transitional disks. The main goal is to resolve the molecular gas inside the holes of transitional disks, using millimeter interferometry with the Atacama Large Millimeter Array (ALMA). The first, surprising result became Van der Marel’s first science publication. Initially, van der Marel dreamt of becoming a writer and later a science writer. ‘After the ­experience of doing my own research and looking at things that nobody had even seen or done before, I truly became passionate with research.’

“The original idea was studying the gas around the star,” explains Van der Marel in her office in the Huygens-building.

A conference poster is hanging on the wall, showing images of the ‘transition disk’.

In such a disc, dust and gas can cling together and form ever bigger accumulations, pebbles and rocks, finally yielding full blown planets like earth or even Jupiter. That has happened in our solar system. And also around mamy other stars, as has become clear over the last decades, in which more than a thousand exoplanets have been discovered. The exact processes of planet formation, however, are still very much the subject of research.

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ap “Coalescing of dust is a process that takes place over many different length scales. Dust particles smaller than a micro­meter have to grow over twelve orders of magnitude to become earth-size planets. When they grow above 1 km, they start to attract each other by gravitation, but long before that, you have to solve the problem of growing up to 1 millimeter”, says Van der Marel.

For this to happen, dust particles have to collide so they can cling together. But colliding also means that they might fragment into smaller particles, which isn’t beneficial for growth.

“And there is another problem,” adds Van der Marel. “By some subtle gas pressure effects in the disc, gas moves slightly slower than the dust particles. This slows down the dust by friction, so that particles fall down from their orbit, into the star, before they can even start to grow.”

Originally, Van der Marel and her colleagues wanted to image and research the special, ring shaped transition disc around Oph IRS 48 in the constellation Ophiochus. So they applied for observation time on ALMA, the Atacama Large Millimeter/submillimeter Array. ALMA is a new radiotelescope, consisting of 66 separate antenna dishes in the ultra-dry Chilean Atacama desert. It can image radiofrequencies from the universe with wavelengths around a millimeter.

In that stretch of the radio spectrum, several molecules in gas clouds show up by characteristic frequencies. “We wanted to image a particular peak in the gas spectrum,”says Van der Marel, “but by design, ALMA also delivers part of the neighbouring spectrum for free.” That part of the spectrum show dust particles measuring around a millimeter. “We expected that dust to form a ring-shaped cloud as well, but surprisingly, all of it was centered on one side of the star.”

First, Van der Marel and her PhD advisor Ewine van Dishoeck, didn’t understand one bit of it. “We thought: something must have gone wrong, so we checked and we rechecked.”

But the result didn’t go away. “So we switched to: ‘Suppose it is real’”, van der Marel says. The researchers got in touch with Kees Dullemond at the Institute of Theoretical Astrophysics in Heidelberg, Germany, an expert in modelling gas and dust in transition discs. “And he got all excited. ‘This is fantastic’, he said, ‘Exactly what our models predicted.’”

Models of ring-like transition discs where the inner part has been ‘cleaned out’ by an earlier planet, show a certain swirling motion in the gas, called a Rossby instability. Mathematically, it’s a relative of the meandering swirls of air in the atmosphere, but it’s also related to the swirling of creamer in a cup of coffee.

This slow vortex can trap dust on one side of the star, Dullemond’s models predicted. Appropriately calles a ‘Dust trap’, this prevents dust from falling into the star. But, warns Van der Marel, that doesn’t mean that the problem of planet formation has been fully solved now. “As the dust particles grow, they will eventually escape the dust trap “, she says, “and they will spread out in a ring shape again.”

“We’ll certainly do more research into this”, van der Marel says. New observation proposals have been filed already. “We want to look at the disc again, and with better resolution, but we also target transition discs around other stars.”

The Science paper was Van der Marels first publication, “I expect to publish more about this, but this was certainly a huge high point for me. Quite overwhelming.”

Diego Garlaschelli Leiden Institute of Physics

The angle, long before the banking cri The interrelationships between banks were changing long before the recent banking crisis materialized, theoretical physicist Diego Garlaschelli found out when he analyzed data from the Dutch central bank De Nederlandsche Bank. “The discovery was news”, says a modest Garlaschelli. It certainly was – the changes went unnoticed in the analysis methods economists routinely use.

By Anouck Vrouwe “There, three years before the banking crisis exploded. Something’s clearly changing there.” Pointing to an angle in a graph, followed by a downward slope, Diego Garlaschelli recounts: “The transition attracted my and my colleague Tiziano Squartini’s attention. We realized how important it was when De Nederlandsche Bank researcher Iman van Lelyveld showed his enthusiasm for the result. We were collaborating on the project. So we abandoned the original research question, and continued with this.”

Garlaschelli is no economist. He even confesses to knowing ‘very little’ about economic theory. Nonetheless, his latest research paper delves into the stability of inter-bank networks. But Garlaschelli has his desk at Leiden University’s Lorenz Institute for Theoretical Physics. He’s often been asked the ‘why’ question, and has his answer handy: “Economists work with economic theories. They want to understand why the market behaves as it does. I don’t do that. I only study how the economy behaves.” Garlaschelli is an Econophysicist – a researcher who looks at interesting patterns in economic data from a physicist’s viewpoint.

The team-up with the De Nederlandsche Bank came about more or less by chance. A colleague of Garlaschelli’s knew

someone there, and Garlaschellli visited the bank to see if there was any shared ground in the research being done there.

In fact there was: Van Lelyveld was looking into mutual relationships between banks. Banks loan each other money back and forth, and so form inter-bank networks. Garlaschelli happens to specialize on networks. He’s familiar with the best analytical methods for dealing with such networks – methods he himself develops, together with his co-workers. “If I do my job properly, every project turns up two publications. One in theoretical physics, on the methods, and one in the field the methods are being applied in.”

In this case, the theory was already well-developed. Garlaschelli and Squartini wanted to test their analysis method on real data, from actual networks. “We used the banking network here, but I analyze social networks too. And in the past I worked on the stability of ecosystems. Using the same methods. That’s the beauty of my field.”

De Nederlandsche Bank provided Garlaschelli with data on the banking network in the Netherlands; all mutual loans from one and a half million euro and upwards, anonymised.

“No, we weren’t hunting for early signals of the looming bank crisis. We were mostly playing with our methods and their

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isis data”, Garlaschelli confides. But then there was that exciting angle in the graph. A crook the economic models just didn’t spot.

Whereas formerly banks were loaning back and forth, hedging in case the opposite party would go bankrupt, the number of these ‘back-andDiego ­Garlaschelli (1977) forth’ transactions clearly declined from studied Physics in Rome, his 2005 onwards. “For the explanation of birthplace. He took his Ph.D. in these changes, ask the economists. But it Siena, Italy, on ecological networks. has something to do with banks covering He followed this up with research on economic networks, in England and themselves less”, Garlaschelli explains. elsewhere. Garlaschelli came to Leiden “Banks apparently judged their risks in 2011; the university was looking otherwise than before.” for a university lecturer in Econo­ How could economists have overlooked physics. “This is a young field.

It’s nice that positions are these changes? Garlaschelli: “The econobecoming available.” mists at De Nederlandsche Bank also analyze these data, of course. They look at how much the real economy deviates from the models. They noticed a change in the network, too. But that was in 2008.

By then everyone knew the banks were having problems.

We were taking differences between banks into account a little more; that there are a few large banks that have many interactions, and many small ones with less interactions. We claiming we could have predicted the crisis. We’re saying identified the dangerous ‘debt-loops’ that remained invisible that the network changed in an unusual way, following a in the standard analyses.” This is precisely the strong point of period of stability. I would be extra alert, if I were supervinetwork theory, says Garlaschelli: “You study indirect shifts sor.” For actual predictions, Garlaschelli would need more in complex systems, at the same time taking important difdata, covering a longer time period and from other countries ferences between parties into account. These indirect changes as well. “The Dutch banking network is closely entwined with flagged strong warning signals of the coming crisis.” international banks.” Van Lelyveld is now discussing access to foreign counterparts data. In the meantime, Garlaschelli is Could he have foreseen the crisis, where the economists furthering his work on social networks. “That’s fun, too.” failed to do so? “Woah”, Garlaschelli returns. “We’re not

Marco Streng Mathematical Institute

Faster number theor Complex polynomials related to elliptic curves are at the heart of current number theory research. Elliptic curves also have the interest of cryptographers, as they can be used to make cryptographic keys that are hard to break. The research of Marco Streng concerns curves that are more complex than elliptic curves. The related polynomials are too large to work with efficiently, but Streng is developing a method to simplify them.

By: Willy van Strien

During the first years of his studies in Utrecht, Marco Streng (1982) studied both mathematics and computer science, but he found mathematics more fascinating. He came to Leiden for his PhD research in number theory, then moved with his young family to Warwick (UK) for a post doc position, followed by another post doc at VU University Amsterdam. When he won an NWO-Veni grant, he returned to Leiden.

Like many mathematicians, Marco Streng had no interest in mathematics at school. In fact, it was quite boring to him.

But his participation in mathematical Olympiads, and the training before that, changed his mind. He discovered that mathematics was exciting, and now he is involved in challenging problems in number theory, combining analysis, algebra, and geometry with large-scale computer experiments.

To explain his research, he starts with a problem that was solved more than 250 years ago: (which prime numbers can be written as the sum of two squares: p = x2+y2?) “In number theory, we always start with prime numbers”, Streng explains before giving the answer. “For primes are the building blocks of all numbers: every number is the product of primes. They are easier to handle than non-prime numbers.”

It turns out that the prime numbers that can be written as x2+y2 are the sum of any number that can be divided by 4 plus 1. For instance, 5 (4+1) = 22+12; 13 (12+1) = 32+22. So, the prime numbers for which the equation can be solved can be represented by a formula: p = 4a+1.

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ry, safer cryptography Number theory is full of such peculiarities that may seem magic, but that can be explained by theory. There also are formulas that describe the primes that can be written as x2+2y2, or as x2+3y2, etcetera.

Mathematicians wondered how far this goes. They asked for instance: which prime numbers can be written as: p = x2+71y2? And they found formulas to describe the primes that obey such requirements. These formulas are polynomials, sums of several terms that contain different powers of the same variable v, each coupled to a coefficient a (a1, a2v, a3v2, a4v3, and so on).

The polynomial for the equation p = x2+71y2 has eight terms and is surprisingly long. Its coefficients are so large that the formula stretches over several lines, Streng shows: “And when you go further, you get coefficients that have thousands of digits. That is horrible to work with, of course.”

But Heinrich Weber (1842-1913) found a way to reduce the coefficients considerably. Streng: “The original polynomials are based on several symmetries. To reduce the coefficients, one needs to let go of some symmetries. But when removing too many symmetries, everything stops working, so there is a delicate balance.”

The polynomials that solve the x2+...y2 problem come from the theory of elliptic curves, which are curves of the form: y2 = x3+ax+b. Solutions of equations involving these polynomials can be transformed to elliptic curve descriptions, and vice versa. So, by reducing the coefficients in the polynomials, it becomes easier to create these elliptic curves as well.

Elliptic curves are a hot topic in current number theory, but they also have the interest of cryptographers. Currently, websites, data and messages are secured with keys that are

based on the product of prime numbers, which need to have several hundreds of digits to avoid being broken by hackers.

Cryptography based on elliptic curves is an alternative that needs only a few dozen digits. A point on such a curve is agreed upon and operations are performed from this point to generate a secret code. According to Streng, it is as yet impossible to break such a key thanks to the complex algebraic structure of elliptic curves. And because such keys are much smaller than keys that are based on products of primes, communication would be much faster. Reduced coefficients in related polynomials make it possible to construct suitable elliptic curves faster and to construct more of them.

When Streng attends conferences on elliptic curves, he not only meets mathematicians and cryptographers, but also employees of security and information agencies, illustrating the wide interest in elliptic curve cryptography. “The idea is from 1985, and now Google is among the first to apply it”, he says.

His own research is ahead of these developments. It concerns curves that are more complex than elliptic curves, and the related polynomials, which also have very large coefficients.

Streng is trying to find a way to reduce these coefficients, analogous to the work of Weber. “For these curves this is more complex and needs more theory, but patterns are surprisingly comparable”, he tells. He was already able to show that a reduction of coefficients is often possible, and now hopes to design a strong general method.

If he succeeds, this would be an important contribution to number theory, and it would help provide an alternative to elliptic curve cryptography, involving even smaller numbers.

Fons Verbeek Leiden Institute of Advanced Computer Science

Zebrafish, countless zebrafish Do you have more digital pictures than you could ever properly catalog? ­Biologists have a similar problem: their microscopes take image after image. Bioinformaticist Fons Verbeek develops computer software that orders and ­analyzes this digital horn of plenty.

By Anouck Vrouwe Fons Verbeek apologizes for the piles of paper covering the meeting table in his office. “All of the data, all the analysis programs, everything important is in my computer”, he says: “What’s lying here can wait – and then this is what you get.” He had wanted to clear up. But it’s been busy these days, the bioinformaticist explains. Verbeek likes doing several things at once, working simultaneously on several projects. “2013 was a good year. Everything came together.

Methods we had developed for the one project proved suitable for the other – things like that. Many of my PhD students completed their thesis this year. The results of years of work became visible.”

Meanwhile, Verbeek is scrolling through his presentation, conjuring up superb movies of tiny fish with big eyes. The images are built up of green dots or colored surfaces. The fish revolve around their longitudinal axes, can be viewed from any angle. The three-dimensional images are of zebrafish: more precisely, zebrafish embryo’s, transparent little animals that are used in genetics studies and in experiments in the field of developmental biology. Verbeek, pointing to the screen: “Look, here you can see how tuberculosis bacteria are spreading through the fish.”

Verbeek does collaborate closely with biologists who perform these types of studies.

Thanks to better and faster microscopes, biologists can gather more images than ever before. “Beautiful pictures, folders full of them. They still need analyzing, though. The microscope used to be the bottleneck, nowadays the biologist is. You can’t process all that by hand anymore”, Verbeek explains.

Ever growing stacks, just like the papers on his table: too much effort, too little time. Verbeek develops methods that can tackle the microscope images. Sometimes by adapting the microscope’s software. “This microscope rotates the specimen, the better to be able to compare images.” Most often, however, it’s computer programs that retrospectively analyze the footage, automatically. Verbeek demonstrates an analysis program that snips the zebrafish out of an image and measures it’s length. It also recognizes body parts such as spinal chord and eyes. “Just as security firms do face recognition, we do zebrafish recognition”, Verbeek grins. Zebrafish-recognition software, outlandish though it may sound, is in demand.

Verbeek has even started a small company to market the software. “The foundation stands, refining it further is no longer scientific research.”

Not that Verbeek himself studies tuberculosis. His research group, Imaging and Bioinformatics, is part of the Leiden Institute of Advanced Computer Science (LIACS). But

“Wait, this is good too”, says Verbeek, clicking his mouse rapidly. A film starts, showing vague white blobs in a dark background: “Look, cancer cells.” Biologists are interested in

Fons Verbeek (1960) is

Associate Professor. He studied Biology, subsequently training in Computer Science, and taking a PhD in Applied Physics. Verbeek started his research career as a bioinformaticist at the Academic Medical Center (AMC), Amsterdam, moving on to the Hubrecht Institute for Developmental Biology and Stem Cell Research (Royal Netherlands Academy of Arts and Sciences), Utrecht, in 1996. As of 2003, he is group leader Imaging and how mobile the cells are – an indication Bioinformatics at the Leiden Instiof the speed with which the cancer may tute of Advanced Computer spread. The software developed by Verbeek’s Science (LIACS).

group recognizes individual cells and follows them through time, then calculates their speed. “It automates tiresome laboratory work.”

And then there is the Internet. Verbeek emphasizes the importance of new ways of presenting biological research data on the Internet in a comprehensible way. The everrising tide of publications is making it more difficult for scientists to keep an overview of their field of study.

“Research is specialist work, and biologists are often busy on their own little islands, not knowing how their work relates to other research islands. They appreciate having a clear picture of related work on the Internet.”

This is why Verbeek presented a zebrafish digital atlas in 2012, bringing together all the available research. It includes countless high resolution images, with explanatory keys to the body parts on view. The atlas also contains a database of genetic information, facilitating looking up which genes are active at any point in development.

“Presenting the information in a spatial and clear way leads to new insights”, says Verbeek, justifying the mammoth project. “A biologist can for example see that the genes he is studying in the brain are active too in the gut at the same time in development.” And an advantage the digital atlas has over past paper atlases, is that further items of information can easily be added.

The man who is such a stickler for order in the digital world casts another glance at the growing disorder on the meeting table. His clever software doesn’t sort papers.

“Oh well, maybe I should throw the whole of it away.

That’s a form of order too.”

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Sandra Scanu (1981) studied Biotech-

nology in Milano, Italy. Between November 2008 and January 2013, she was a PhD student at the Leiden Institute of Chemistry, where she studied proteinprotein interactions using paramagnetic NMR spectroscopy. She is currently a postdoc researcher at the Technische Universität München, Germany. ‘My main scientific interest is to understand what is really going on in living cells. There are so many biochemical processes taking place at the same time, with such perfect coordination – and together they give rise to life!’

Sandra Scanu Leiden Institute of Chemistry

How proteins meet and Theory had already predicted it, but no one had been able to prove it in the lab: that certain protein complexes are held together not only by electrostatic forces, but also by hydrophobic interactions. Sandra Scanu was the first to produce the experimental evidence.

By Nienke Beintema Proteins play a vital role in virtually all biological processes.

From growth and reproduction to pathogen defence and molecule transport: proteins are the ‘workhorses’ of all ­living systems. They rarely work alone. Usually they join forces to form intricate, three-dimensional complexes with very specific tasks. But how do proteins find and recognize each other? How do they balance speed and specificity when joining forces? And, ultimately, how can we relate mistakes in this process to human diseases? The answers to these and similar fundamental questions help scientists to unravel the molecular mechanisms that lie at the basis of life.

“Over the years, scientists have made various theoretical ­models that describe how proteins recognize each other and then bind”, says Sandra Scanu, who just finished a PhD ­project at the Leiden Institute of Chemistry. “These ­models are based on the different forces that act between the ­molecules.” These can be electrostatic forces, as she explains, which result from local charge differences. They can also be hydrophobic forces, which act between amino acids on the outside of the proteins. These amino acids are hydrophobic: they repel water, and therefore tend to cluster together with other hydrophobic amino acids.

Although theoretical models have proposed a leading role of hydrophobic forces in protein complex formation, scientists had never been able to prove this experimentally. All proven models describe protein interactions solely driven by electro-

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bind static forces. “The hydrophobic interactions are much trickier to identify”, says Scanu. “This is because they are difficult to measure, and also because it is a challenge to describe them in mathematical terms.” Yet Scanu, her supervisor Marcellus Ubbink and other colleagues succeeded in showing the presence of hydrophobic forces in protein interactions. They used a unique multidisciplinary approach: they combined advanced NMR spectroscopy with computational techniques that simulate protein interactions.

Quick transition

Protein complex formation is a stepwise process. While the free components evolve to the final complex, they pass through a so-called encounter state. The transition through this intermediate state increases the probability that a productive complex can be formed, because it helps the proteins to find the right orientation relative to each other. Scanu studied the encounter complex that is formed in the association between plastocyanin and cytochrome f: two proteins that play an important role in electron transfer during photosynthesis. This is the process by which plants and cyanobacteria use sunlight to convert carbon dioxide and water into sugar and oxygen.

Electron transfer complexes such as plastocyanin/cytochrome f are notoriously difficult to study, as Scanu explains, because they form very fast, in a matter of milliseconds. Scanu used a specific type of nuclear magnetic resonance (NMR) spectroscopy to track this process: paramagnetic relaxation enhancement (PRE) NMR spectroscopy. NMR in itself is a technique to identify atoms in a molecule on the basis of their electromagnetic properties in a magnetic field. Atoms in a molecule absorb and re-emit electromagnetic radiation in a typical pattern. This pattern can be visualised in a spectrogram, which yields a unique ‘fingerprint’ for each molecule. In com-

bination with PRE, this technique also provides information about the distances between atoms, in this case the atoms in two different proteins. “Using this information in combination with computational simulations”, says Scanu, “we can reconstruct exactly how the two proteins are positioned relative to each other during their bonding process.”

It turned out that there was no clear distinction between the encounter complex and the active complex. “Our data showed that in the encounter state, plastocyanin makes hydrophobic contacts with cytochrome f, allowing a quick and efficient transition from the encounter complex to an active complex”, explains Scanu. “I believe that this model can also be applied to other systems involving multiple interaction partners, for instance proteins involved in signal transduction.”

Acclaim

Scanu published her findings in the prestigious Journal of the American Chemical Society (April 2013). Among other things, her research was awarded a prize at the International Conference on Magnetic Resonance Microscopy in Lyon, France (August 2012). “I think this is mostly because of the unconventional multidisciplinary approach that we used”, says Scanu. “We feel lucky that it worked out this way.”

And although she was able to propose a new model to describe protein complex formation, Scanu acknowledges that some pieces of the puzzle are still lacking. “We still need to understand the individual roles of the different hydrophobic amino acids”, she says. “Some could be more important than others. Yes, these are also very fundamental questions. How are hydrophobic interactions modulated in living systems?

You have to understand this on a fundamental level before you’ll be able to manipulate the process.”

Gerard van Westen Leiden Academic Centre for Drug Research

Computer power in the hunt for new Bringing together information on the properties of ‘small molecules’ and their targets in the computer makes fast identification of potential new drugs possible and can help reduce side effects. Gerard van Westen: “The approach makes use of the ongoing exponential growth in computer power and the increasing availability of public databases containing the necessary information.”

By Marcus Werner Stupendous numbers of small molecules are theoretically possible. The class of, literally, relatively small organic compounds has since the 20th century been the dominant source of pharmaceuticals. In general, small molecules bind to protein ‘targets’ in living cells, thereby either promoting or inhibiting their activity. In fact this is how most drugs exert their effect in treating illness and disease. But just a minute fraction of small molecules have actually been made in the lab, and even fewer are currently in use as drugs. Computational chemists like Van Westen ‘train’ computer models to sift through ‘libraries’ of existing small molecules with unknown ‘bioactivity’, even those that only exist virtually in the computer, and look for potential new drugs. Such searches were until recently mainly based on the concept of ‘molecular similarity’ – small molecules that are similar in chemical structure are most likely to have similar biological effects and be useful as drugs. Van Westen has taken the concept a step further by also taking the molecular similarity of target proteins into account: “That way, you get a better handle on the interaction between potential drugs and the proteins they’re aimed at.”

Van Westen didn’t originally plan to be a computational chemist: “I wanted to study medicine, but discovered that the training is mainly focused on making a diagnosis and less on research. Doing medical research attracted me, and I opted

for Bio-Pharmaceutical Sciences at Leiden University.” Leiden University at the time was the sole Dutch university offering a Master’s program in this field – coincidentally in Van Westen’s home town. Disappointing results in Van Westen’s first research project during a nine-month internship at the Leiden Academic Centre for Drug Research (LACDR) set him off towards his future calling: “We were investigating how a particular protein involved in vascular disease interacts with blood vessel walls, but just couldn’t hit on the binding location. A friend in the Bio-Pharmaceuticals student’s association ‘Aesculapius’ suggested e-mailing someone he knew was involved in computational methods in the pharmaceuticals industry.”

It proved to be a springboard to an internship with the Tibotec pharmaceuticals company in Belgium, where Van Westen used computational methods in research on anti-HIV drugs: “I decided that this was what I wanted to do.”

The Belgian sojourn led to a Tibotec-funded PhD position at LACDR, on predictive computational models using small molecule and protein similarities simultaneously, dubbed ‘Proteochemometric modeling’ (PCM). Much of the research is published in top ranking journals. One study focused on HIV – the virus causing AIDS. Although incurable, AIDS is now controlled by combinations of several anti-viral drugs.

The anti-viral cocktail used for a particular patient is based on

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w drugs the genetic ‘fingerprint’of the infecting viral strains, which in turn determines the properties of the viral proteins targeted by drugs. In this way drugs to which the strains are resistant can be avoided. By including data on drug similarities as well as viral genomes in a PCM model, Van Westen achieved a high correct resistance prediction rate, as well as identifying 17 as yet unpublished resistant viral strains. “Predictions like these could be used for provisional treatment before viral resistance is determined in the lab, which takes time.” Another study tackled a class of related cell-surface proteins which are targets in the treatment of a number of diseases, including diabetes and Parkinson’s Disease. A PCM model including some 11,000 small molecules and several of the targets turned up six novel small molecules, the activity of which was confirmed experimentally. Van Westen: “Typically drugs bind to several similar protein targets, but that have different functions. Side effects are the result. Studies like this can help identify more specific drug-target interactions and cap side effects.”

Van Westen is continuing his computer-aided quest for novel drugs at the European Bioinformatics Institute in Cambridge, UK. One line of research concerns protein targets of the human influenza virus, in collaboration with researchers in Grenoble, France: “Instead of the highly variable proteins on the outside of the virus, we’re looking at targets inside which are shared by all strains. That could lead to more universal influenza vaccines.” Asked as to what he would be proud to do on completion of the Cambridge project in 2015, Van Westen muses: “Returning to Leiden would be ideal. Settling down there would be good for my two children’s schooling. And I like an academic setting. Explaining things to students helps my thinking, too.”

Gerard van Westen (1983) studied

Bio-Pharmaceutical Sciences in Leiden. Following a PhD in computational chemistry (Leiden Academic Centre for Drug Research, 2013), Van Westen currently works as a post-doctoral researcher in Cambridge, UK (Marie Curie/ European ­Molecular Biology Laboratory ­Fellowship).

From his study time at Utrecht University,

M ­ aurijn van der Zee (1976) has been interested in animal evolution and embryonic development. During his PhD in Keulen (Germany), he discovered the potentials of the red flour beetle as a model organism for this research field. In 2010, after a few post doc positions, he came to Leiden with a NWO-Veni grant – and brought the beetles with him. He now is assistant professor on a tenure track position. Chris Jacobs (1986) joined him, first as a master student and then for his PhD research. Jacobs’ interest in biology has been evident from childhood. After finishing his thesis, he intends to apply for a post doc position abroad.

Maurijn van der Zee en Chris Jacobs Institute of Biology Leiden

Thanks to an innovative egg Biologists Maurijn van der Zee and Chris Jacobs identified one of the key factors that made the insects flourish on earth.

In contrast to their marine ancestors, insect embryos enfold themselves in a second membrane within the maternally derived egg shell. The two showed that this second membrane, the serosa, prevents the eggs from drying out. It is an evolutionary novelty that freed the insects from the need to live close to water and enabled them to disperse over land.

by Willy van Strien The insects have done extremely well since their ancestor left the sea to invade the land, five hundred million years ago. It is difficult to overestimate the changes that are needed to turn a marine animal into a terrestrial one.

So, it is no wonder that the insects underwent radical modifications after descent from their marine ancestors.

A novel egg design is one of those. All arthropods, the animal group to which the insects belong, have eggs in which embryo develops within the maternally derived egg shell. But only the insect embryos surround themselves with two membranes below this egg shell, the amnion and the serosa. The embryos of chelicerates (spiders, scorpions, mites), myriapods and crustaceans (crabfish, lobsters, shrimp, prawn) do not.

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design, the insects populated the continents Maurijn van der Zee first wanted to find out how the serosa is formed. More generally, he was fascinated by the question how to ‘make another animal’ by modifying genes that control embryo development. “Since decades, Drosophila has been the model species for biological research and become a very well-known animal”, he tells. “Now it was interesting to turn to another insect species. A good candidate was the red flour beetle, Tribolium castaneum. Its genome had been sequenced and molecular tools were available for experiments.”

In this species, he unraveled the genetic background of the serosa, and next came the question: ‘why?’ Van der Zee: “It is nice to study genes and their influence on embryo development, but I also wanted to know about the ecological relevance of characteristics. So, what function has the serosa of the insect egg?”

A probable answer, he realized, was that the serosa prevents the embryo from desiccation. For in related arthropod groups that lack it, the eggs are not exposed to dry conditions. Spiders wrap their eggs in isolating silk and mites cover their eggs with a wax coating; the eggs of scorpions remain within their mother’s body until after hatching; myriapod eggs develop in moisty soil and litter; and crustaceans inhabit the sea.

The best way to test whether the serosa might be an anti-desiccation device, would be to remove it from insect eggs and see what happens. But this may seem impossible as the embryo and its membranes are surrounded by the maternal egg shell, and that cannot be removed without damaging the egg.

Still, there is a way out. Van der Zee had discovered that the development of the serosa is under control of just one single gene: zerknüllt1 (also known as Tc-zen1). A molecular technique (RNA interference) is available to inactivate this gene by degrading its transcription product, the messenger RNA.

“When you inject the appropriate RNAi-molecules in female pupae, the expression of zerknüllt1 will be suppressed in all her cells, including the egg cells”, he explains. “Later, after fertilization, a serosa will not be formed in these eggs.”

Surprisingly, these serosa-less eggs develop well – but only in moist laboratory conditions. At low humidities, the embryos dry out.

The serosa secretes a cuticle, consisting of chitin. Also this process is under control of one gene, Tc-chitin-synthase1 (also known as Tc-chs1). Chris Jacobs suppressed this gene in the same way that zerknüllt1 was suppressed in the previous experiments. “Eggs with a serosa that doesn’t form a cuticle also die at low humidities”, he tells. “So, it is the cuticle that protects the embryo against desiccation.”

The serosa appeared to have other functions as well. Also at high humidities, Van der Zee and Jacobs learned, eggs without this membrane fail to hatch. How is this? At the end of embryonic development, the membranes actively pull the sides of the embryo over the yolk and close the back of the embryo. When the serosa is absent, the amnion has to perform this task alone. But at high humidities the egg becomes water-logged, and the amnion is not strong enough to close the swollen embryo. In such conditions, the serosa is needed for proper dorsal closure. Next to this, the serosa triggers the immune system, protecting the embryo from microbial infections. “And it may prevent mechanical damage and predation as well”, Van der Zee adds.

“A particular group of flies, the Schizophora to which Drosophila belongs, lost the serosa”, Jacobs tells. “Notably, those flies deposit their eggs on moist places, such as rotting plant material. They are the exception that supports our findings.”

Laura Bertola Institute of Environmental Sciences

Two distinct groups of African lions Laura Bertola’s specialty is phylogeny: the genetic relationships between groups of animals within a species. African lions, as she discovered, actually comprise two distinct genetic lineages. This discovery has important implications for conservation.

By Nienke Beintema In historic times, lions used to be widespread not only across Africa, but also in large parts of Southern Europe, Asia Minor and far into India. Today, they are almost exclusively found in Sub-Saharan Africa. Some smaller populations are found in West and Central Africa – and one threatened population remains in a national park in Northwest India.

African lions and Asian lions are classified as two different subspecies. “Historically, such taxonomic distinctions were made on the basis of geography and morphology”, says biologist Laura Bertola at the Leiden Institute of Environmental Sciences. “But in some cases this approach gives a poor representation of the actual diversity within species.” Asian lions, for instance, are generally smaller than the lions of Southern and East Africa. They live in smaller groups and prefer smaller prey. But these traits are also found in the lions of West and Central Africa. Moreover, such characteristics are sometimes flexible. Bertola: “Lions are very adaptable. Under different circumstances, they shift to different prey species and group sizes.” In short, the distinction between subspecies sometimes turns out to be arbitrary. This is why modern scientists, including Bertola, take a different approach: rather than relying on morphology, behaviour or geography, they use the latest genetic tools to refine – and sometimes redefine – these ‘old’ taxonomic groups.

Bottleneck

Bertola collected DNA samples by collaborating with researchers working on other lion topics throughout Africa. She sometimes joined them on their expeditions, but mostly worked from Leiden, receiving her samples in the mail – blood samples, but occasionally lion droppings as well. Joining forces with the Leiden Institute of Biology (IBL), she combined different genetic approaches to map the genetics of Africa’s lions.

This research showed an interesting fact: the lions of West and Central Africa are genetically more similar to Asian lions than to the lions of Southern and Eastern Africa – as predicted by their morphology and behaviour. “This suggests”, she says, “that the two African groups have a different history. Perhaps at some point in time, lions were extinct outside of East and Southern Africa, and they recolonized West and Central Africa from populations in the Middle East.” This hypothesis is supported by the fact that the lions of West and Central Africa show relatively little genetic diversity. This is characteristic of populations that have gone through a so-called bottleneck, which means that the current population is descended from a relatively small founder group.

Conservation

The distinction between the two African lion groups is important for conservation, she emphasizes. But why exactly?

Laura ­ ertola (1984) B

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received her MSc degree in biology at the University of ­Leiden in 2008. Since 2010, she has been conducting PhD research at the Leiden Institute of Environmental Sciences (CML), focusing on the genetic relationships between African lions. ‘Although most of my work takes place in Leiden, I’m very happy that I’ve also had the chance to study lions in the field. Everything I’d read about the species and the ecosystem suddenly made sense. If you are passionate about conservation, Bertola smiles. “It depends on what you’re you have to go and see the system trying to conserve. If you just want to make and talk to the people who are living in it.’ sure that lions survive on earth, it doesn’t mat-

ter. But in general, the principle is that we want to conserve as much genetic diversity as possible. This calls for a different perspective, a different set of priorities.”

As an example, she names the fragile position of the lions of West Africa. Populations are relatively small and under threat due to hunting and habitat loss. In addition, these lions’ low genetic diversity makes them vulnerable to inbreeding and disease. “Suppose you wanted to boost some of these populations by translocating animals into this area”, she says. “The best choice would be to take lions from the same genetic group – in this case, from West or Central Africa – rather than animals from Southern Africa.”

Similarly, such genetic information is helpful in breeding programmes in zoos. “There is no a studbook for African lions in captivity”, she says, “which means that we often have no idea where they came from and how they are related. But if you ever want to reintroduce captive lions into the wild to support conservation efforts, you want to keep the genetic lineages as ‘pure’ as possible.” Now that West African lions have turned out to be different from Southern African lions, they should preferably not interbreed in captivity, Bertola suggests. “But it is a complicated matter”, she acknowledges. First of all, in practical terms: “We don’t know the genetic makeup of captive lions – they are probably a mixture. We would have to take DNA samples of many lions in captivity, and maintain detailed family trees into the future, which is costly and timeconsuming.” Secondly, she points out, these purity arguments are subject to debate. Around 20.000 years ago, the two cur-

rent genetic lineages were still one, so why preserve the two groups separately today? In addition, it is still unclear how this genetic diversity translates into the animals’ health and wellbeing in nature.

Much of Bertola’s research is fundamental, as she concludes.

She is trying, for instance, to relate the biogeographical history of the species to climatic conditions. “But my main motivation is its potential for conservation – perhaps not today, but certainly sometime in the future.”

Awards and Prices in 2013 research Leiden Institute of Biology Leiden Institute of Chemistry Leiden Institute of Physics Leiden Observatory Leiden Observatory Leiden Observatory Mathematical Institute Mathematical Institute Mathematical Institute Hortus botanicus Leiden Academic Centre for Drug Research Faculty of Science Institute of Biology Leiden Institute of Environmental Sciences Leiden Academic Centre for Drug Research Leiden Academic Centre for Drug Research Leiden Academic Centre for Drug Research Leiden Academic Centre for Drug Research Leiden Institute of Physics

Prices and Honours

Dr. Rinny Kooi received a Royal Decoration 'Knight in the Order of Oranje Nassau' Prof.dr. Marc Koper received the Carl Wagner Memorial Award 2013 Dr. Wessel Valkenburg won the final of the Ig Nobel competition 2013 Prof.dr. Michael Garret received aIBM Big Data and Analytics Faculty Award Dr. Rychard Bouwens received the Pastoor Schmeitsprijs for Astronomy 2013 Prof.dr. George Miley was honoured with an honorary Fellowship of the Royal Astronomical Society Phd student Eric Siero received the ‘Red Sock Award’ for best Poster Presentation at the SIAM applied Dynamical Systems Conference in Utha, USA Prof.dr.ir. Bert Peletier received a Royal Decoration 'Knight in the Order of the Netherlands Lion' Drs. René Pannekoek received the Philips Math Award for Phd students

Special Funding

Hortus Botanicus Leiden participates in the 'Dutch Society of Botanical Gardens' which received 2 million euros from the "Nationale Postcode loterij" for 'Planten voor de toekomst' The Leiden Academic Centre for Drug Research participates in the 'European Lead Factory' an international multi million project

Appointments

Prof.dr. Han de Winde was appointed as Vice-Dean Faculty of Science and as professor 'Industrial Biotechnology’ at the Institute of Biology Leiden Prof.dr. Menno Schilthuizen was appointed as professor ‘Character evolution and biodiversity’ Prof.dr. Arnold Tukker was appointed as professor Industrial Ecology' and Director of the Institute of Environmental Sciences Dr. Elizabeth de Lange was appointed as Fellow of the American Assosiation of Pharmaceutical Scientists Prof.dr. Arnoud Sonnenberg was appointed as professor ‘Cell Adhesion in health and disease’ Prof.dr. Jos Jonkers was appointed as professor ‘Molecular Experimental Oncogenetics and Cancer Therapeutics’ Prof.dr. Joke Bouwstra was appointed as member of the Royal Netherlands Academy of Arts and Sciences Prof.dr. Jan van Ruitenbeek was appointed as chair of the Dutch Association of Physics (Nederlandse Natuurkundige Vereniging) and Fellow of the American Physical Society

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Leiden Observatory Mathematical Institute Mathematical Institute Mathematical Institute Mathematical Institute

Leiden Academic Centre for Drug Research Leiden Institute of Chemistry Leiden Institute of Chemistry Leiden Institute of Chemistry Leiden Institute of Chemistry Leiden Institute of Chemistry Leiden Institute of Chemistry Leiden Institute of Physics Leiden Institute of Physics Leiden Institute of Physics Leiden Observatory

Prof.dr. Huib Jan van Langevelde was appointed as professor ‘Galactic Radio- astronomy’ Prof.dr. Frank den Hollander was appointed as Fellow of the Institute of Mathematical Statistics Prof.dr. Ronald Cramer was appointed as member of the Royal Netherlands Academy of Arts and Sciences and as a Fellow of de International Association for Cryptologic Research (IACR) Prof.dr. Rob Tijdeman was appointed as honorary member of the Royal Mathematical Society Prof.dr. Manjul Bhargava, Prof.dr. Frank den Hollander and Prof.dr. Hendrik Lenstra were appointed as ‘Inaugural Class of AMS Fellows’ of the ‘Fellows of the American Mathematical Society program’

Grants

Dr. Mario van der Stelt and dr. Laura Heitman recieved an ECHO-STIP-funding for their project ‘Novel target engagement biomarkers for better drug candidates’ Prof.dr. Jacques Neefjes (The Netherlands Cancer Institute and Leiden University), prof.dr. Hermen Overkleeft and colleagues received a Gravitation Grant from NWO for their proposal 'ICI - Institute for Chemical Immunology' Dr. Ludo Juurlink and prof.dr. Marc Koper's team received funding for research of CO2-neutral fuels from the Netherlands Organisation for Scientific Research (Nederlandse Wetenschaps Organisatie - NWO) Prof.dr. Geert-Jan Kroes received an ERC Advanced Grant for his proposal 'Towards a chemically accurate description of reactions on metal surfaces' Prof.dr. Gijs van der Marel received an ECHO-funding for his project ‘Synthesis of glycopeptides and phosphoglyceropeptides to characterize and detect posttranslational modifications of Neisseria pili' Prof.dr. Marcellus Ubbink received an ECHO-funding for his project ‘Understanding protein complex formation: The role of the encounter complex’ Dr. Sascha Hoogendoorn received a Rubicon grant to do research at Stanford University ‘Netherlands Magnetic Resonance Research School’ received 800.000 euros funding from NWO for the training of young researchers Prof.dr. Michel Orrit received an ECHO-funding for his project ‘Magic wand: Enhancing single weak emitters in the near field of a gold nanorod’ Dr. Jörn Venderbos received Rubicon grant to do research at Massachusetts Institute of Technology Dr. Michiel Hogerheijde, prof.dr Xander Tielens, prof.dr. Huub Rottgering, dr. Jelle Kaastra and dr. Ivo Labbé received 4 TOP grants from NWO

Leiden Observatory Leiden Observatory Mathematical Institute

Mathematical Institute

Leiden Academic Centre for Drug Research Leiden Institute of Physics Leiden Observatory Mathematical Institute

Universe Awareness (UNAWE) received funding for an educational project from the Gratama Foundation and LUF Dr. Edith Fayolle received a Rubicon grant to do research at Harvard University Prof.dr. Frank den Hollander and colleagues from the University of Amsterdam, Eindhoven University of Technology and 'Centrum voor Wiskunde & Informatica (CWI - Center for Mathematics and Computerscience) received a Gravitation Grant from NWO for their proposal 'Networks' Dr. Frits Veerman received a Rubicon grant to do research at the University of Oxford

NWO Talent Scheme Grants Veni

Dr. Rawi Ramautar for his project ‘Probing a new volume regime in metabolomics with capillary electrophoresis-mass spectrometry’ Dr. Daniela Kraft for her project 'Spherical mosaics of various tiles' Dr. Catherine Walsh for her project ‘From Molecules to Planets: Exploring the Chemical Heritage of Solar Systems’ Dr. Peter Bruin for his project 'Concrete methods in geometry and number theory'

Vidi

Leiden Academic Centre for Drug Research Leiden Institute of Biology Leiden Institute of Chemistry Leiden Observatory

Prof.dr. Catherijne Knibbe for her project 'Predictable variation in children’s dosage'

Leiden Academic Centre for Drug Research Leiden Institute of Physics Leiden Institute of Physics

Dr. Miranda van Eck for her project 'Reversing cardio-vascular disease'

Leiden Institute of Chemistry Institute of Biology Leiden

Dr. Marthe Walvoort received the C.J. Kok Public Award 2012 Dr. Wouter Halfwerk reveived the C.J. Kok Jury Award 2012

Hortus botanicus Lorentz Center

Our Hortus botanicus attracted more than 120.000 visitors, a new record!

In 2013 the Lorentz Center hosted 65 international workshops, of which 23 were held in the new facility Lorentz@Snellius

Dr. Dennis Claessen for his project 'Improving tiny enzyme factories'' Dr. Anjali Pandit for her project 'In the form of photoregulation' Dr. Alessandro Patruno for his project ‘The densest matter in nature’

Vici

Prof.dr.ir. Tjerk Oosterkamp for his project 'Unravelling proteins by 'feel'' Dr. Koenraad Schalm for his project ‘Applied String Theory: Explaining Quantum Matter with Black Holes’

C.J. Kok Awards

Other

C.J. Kok Jury Award Nominees best PhD Thesis of 2013

FIC

TANGO TO TRAF

itions noisy urban cond consequences of in birds A field study into ship interactions for acoustic court

Wouter

Halfwerk

In 2012 the jury decided to award Wouter Halfweg the C.J. Kok Jury Award for his the thesis ‘Tango to traffic, a field study into consequences or noisy urban conditions for acoustic courtship interactions in birds’. In her report the jury stated that Wouter’s thesis reflects a high level of inventiveness. Although his thesis is fundamental in nature, it also increases our understanding of the impact of anthropogenic noise on the acoustic communication between males and females tits and the relationship with reproduction in urban areas. All the chapters of his thesis have been published in leading scientific journals.

Thesis of the Faculty of Science can be found in the Leiden Repository via https://openaccess.leidenuniv.nl

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C.J. Kok Jury Award Nominees best PhD Thesis of 2013 Simulating the cosmic distribution of neutral hydrogen and its connection with galaxies

Alireza Rahmati Leiden Observatory Keywords: Galaxy formation and evolution, Neutral hydrogen, Simulation Radiative transfer The neutral hydrogen distribution and its evolution is closely related to various aspects of star formation. This makes understanding and modeling the HI distribution critically important for studying galaxy evolution. The main focus of this thesis is therefore the study of the cosmic distribution of neutral hydrogen using hydrodynamical cosmological simulations. To do this, we combine hydrodynamical cosmological simulations based on the OverWhelmingly Large Simulations (OWLS; Schaye et al.

2010) with accurate radiative transfer, and account for different photoionizing processes. Then, we study the cosmic distribution of HI and its evolution.

Furthermore, we study the physical connection between neutral hydrogen and galaxies by analyzing the distribution of HI absorbers with respect to galaxies close to them.

Holography, fermi surfaces and criticality Mihailo ÄŒubrovic Leiden Institute of Physics Keywords: AdS/CFT, Black hole physics, Quantum criticality, Unconventional superconductivity We employ the novel method of AdS/CFT correspondence to study strongly correlated fermions, their ground states and the phase transitions between them. AdS/CFT maps the quantum manybody problem to a classical gravity problem, making it more tractable. We find a holographic description of Fermi liquids and then proceed to find novel non-Fermi liquid ground states. In the future one can expect AdS/ CFT to contribute toward our understanding of real world materials.

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Pulses in singularly perturbed reactiondiffusion systems

Frits Veerman Mathematical Institute Keywords: Pattern formation, Singular perturbations, ­Dynamical systems When you start to work with symbols and formulas, and thereby gain some experience in reading them, you’ll notice that these symbols (and the ideas they represent) become more tangible. More and more, you get an idea of what that symbol stands for. You get a feeling of how a symbol behaves, how it reacts to other symbols, what is does. Then, you can start to shove them around, manipulate them, and introduce new symbols because that’s the best way to explain what you found – and suddenly, you’re doing mathematics.

In this thesis, the existence and stability of pulse solutions in two-component, singularly perturbed reaction-diffusion systems is analysed using dynamical systems techniques. New phenomena in very general types of systems emerge when geometrical techniques are applied.

Exceptional model mining Wouter Duivesteijn Leiden Institute of Advanced Computer Science Keywords: Exceptional model mining, Supervised local pattern mining, Regression Bayesian networks, Subgroup discovery Finding subsets of a dataset that somehow deviate from the norm, i.e. where something interesting is going on, is a classical Data Mining task. In traditional local pattern mining methods, such deviations are measured in terms of a relatively high occurrence (frequent itemset mining), or an unusual distribution for one designated target attribute (subgroup discovery). These, however, do not encompass all forms of “interesting”. To capture a more general notion of interestingness in subsets of a dataset, we develop Exceptional Model Mining (EMM). This is a supervised local pattern mining framework, where several target attributes are selected, and a model over these attributes is chosen to be the target concept. Then, subsets are sought on which this model is substantially different from the model on the whole dataset.

E.g., we can find parts of the data where two target attributes have an unusual correlation, a classifier has a deviating predictive performance, or a Bayesian network fitted on several target attributes has an exceptional structure. We will discuss some real-world applications of EMM instances, including using the Bayesian network model to identify meteorological conditions under which food chains are displaced, and using a regression model to find the subset of households in the Chinese province of Hunan that do not follow the general economic law of demand.

C.J. Kok Jury Award Nominees best PhD Thesis of 2013 Biomass electrochemistry : from cellulose to sorbitol Youngkook Kwon Leiden Institute of Chemistry Keywords: Electrochemistry, Biomass, Catalysis, Electrocatalysis, Hydrolysis, Hydrogenation Aqueous phase reforming The primary goal of this thesis is to study the potential role of electrochemistry in finding new routes for sustainable chemicals from biomass in aqueous-phase solutions. In order to assess the potential of electrochemistry in biomass conversion, we developed an online HPLC system by using a fraction collector with a micrometer-sized sampling tip placed close to the working electrode, with the collected sample fractions subsequently analyzed in an offline HPLC system.

To demonstrate this method, we applied it to the poly-ols, i.e. glycerol (C3H8O3), electrooxidation on Au and Pt electrodes at different pH conditions, visualizing the concentration changes of glycerol and its reaction products in correspondence with the current measured in voltammetry, which brought us a concept to co-generate hydrogen and valuable chemicals (i.e. glyceraldehyde, glyceric acid, dihydroxyacetone, formic acid) with high selectivity depending on the applied potential. In addition, we aimed at single-cell synthesis of sorbitol from cellulosic material by generating glucose as an intermediate species. This thesis has demonstrated the separate reactions of cellobiose hydrolysis to glucose by acid and hydroxyl radical on an anode and glucose hydrogenation to sorbitol on a cathode in an electrolysis cell.

Delineating the DNA damage response using systems biology approaches Louise von Stechow Leiden Academic Centre for Drug Research Keywords: Cancer, DNA damage ­response, Embryonic stem cells, High throughput screening, Metabolomics, RNAi screening, Systems biology, ­Translation, Wnt signaling

Cellular responses to DNA damage are highly variable and strongly depend on the cellular and organismic context.

Studying the DNA damage response is crucial for a better understanding of cancer formation and ageing as well as genotoxic stress-induced cancer therapy. To do justice to the multifaceted cellular changes, elicited by DNA damage, use of high-throughput techniques and integration with bioinformatics tools is of great value. This thesis summarizes recent advances in the field of systems biology studies of the DNA damage response and furthermore shows integrated approaches of the study of DNA damage response signaling networks in embryonic stem and cancer cells. By integration of transcriptional changes and the phosphorylation and metabolic response of cisplatin-treated embryonic stem cells, with RNAi-based knockdown screens we identify novel DNA damage response signaling networks, linking process such as Wnt signaling, translation arrest or altered metabolic pathways to the cellular response to DNA damage. Furthermore, genes, whose knockdown sensitizes embryonic stem cells to DNA damage-induced killing, are tested in cancer cells of varying genetic backgrounds identifying a small subset of genes, which represent potential drug targets for sensitization of cancer cells. Altogether, our systems approach for studying the DNA damage response identifies novel DNA damage-induced signaling networks and molecules, which modulate survival in the presence of DNA damage, potentially providing new targets for therapeutic intervention or biomarker discovery.

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Innate host defense against intracellular pathogens Michiel van der Vaart Institute of Biology Leiden Keywords: Innate immune system, Tolllike receptors, MyD88, Bacterial infection, Autophagy, Tuberculosis, Zebrafish model organism This thesis focuses on the recognition of pathogenic bacteria and the defense mechanisms that are activated during the innate immune response to infection. Detection of pathogens, such as bacteria, viruses, and parasites, depends on receptors that bind to evolutionary conserved structures on their surface. The most extensively studied class of immune receptors is the Toll-like receptor (TLR) family, which signals via adaptor molecules such as myeloid differentiation factor 88 (MyD88) to initiate gene expression and activate the appropriate response upon recognition of a pathogen. We have used the zebrafish as a model organism to study how MyD88 orchestrates the immune response against intracellular bacterial pathogens like Mycobacterium marinum, the causative agent of tuberculosis disease (TB) in fish. We found that several defense mechanisms against TB are highly dependent on MyD88, including autophagy, cytokine and chemokine production, and the generation of microbe killing radicals. These findings in the zebrafish model will hopefully aid in the development of new therapeutic strategies against multi-drug resistant tuberculosis infections.

Raptors in changing West African savannas: the impact of anthropogenic land transformation on populations of Palearctic and Afrotropical raptors in northern Cameroon Buij, Ralph Institute of Environmental Sciences Keywords: Raptors, Conservation, Cameroon, Palearctic migrants, Sedentary species, Land-use change, Reproduction, Diet, Foraging

Raptors in West Africa’s savannas have strongly declined the past four decades and many species now survive only in a few pockets of intact habitat, mostly inside protected areas, while some species are on the brink of extinction. Little is known about the processes that sustain raptor populations within increasingly human-transformed savanna landscapes, and clues to the mechanisms and causal drivers behind population declines remain little studied. Moreover, it is unclear how changing conditions differently affect the diverse assemblage of Afrotropical and Palearctic raptors, which depend on the West Africa’s savannas for part or most of their life cycle, and how vulnerability, or adaptability to changing environments, relate to life-history traits such as their mobility, sex, age, body mass, and diet. This thesis quantifies the effects of land transformation on distribution, foraging, diet, and reproductive output of Palearctic and Afrotropical raptors, both migratory and sedentary, in West African savannas, to increase the knowledge that can support conservation efforts directed at the persistence of rich raptor populations in this part of the world.

Faculty Award for Education 2013

In 2013 no less than nine of our teaching staff members have been nominated by our students for the Faculty Award for Education. They have been nominated for a variety of reasons but all nominees are praised for their commitment and enthusiasm.

The chairs of the study associations and the assessor from the faculty board ultimately decide who will be granted the award. The assessor will present the award at the Faculty’s New Year’s reception.

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Prof.dr. Joop Schaye Leiden Observatory Nominated for course(s): MSc Stellar Structure and Evolution A subject in which virtually the entire world of physics comes together is a major challenge for a teacher to impart. Such a subject is ‘Stellar Structure and Evolution’ in the mandatory section of the Master’s programme Astronomy. Not only is Prof. Schaye able to communicate the theory well, but he also succeeds in engendering sound knowledge and enthusiasm for the wondrous way in which physical phenomena form a cohesion. The students call his teaching method retro-innovative, or an excellent user of classic teaching materials. With nothing more than a piece of chalk and a blackboard virtually all of physics is covered, leading to far-reaching discussions on the theory and a crystal-clear rendition of the complex theory. Digital resources are only deployed when this becomes necessary to understand the physics.

Prof.dr.ir. Tjerk Oosterkamp Leiden Institute of Physics Nominated for course(s): BSc Experimental Physics, BSc Fourier Physics, MSc Supercon­ ductivity Tjerk visibly enjoys giving lectures. Through the use of a variety of resources to illustrate the material, and his own enthusiasm, he is also able to enthuse the students. Tjerk attaches a great deal of importance to the student’s insight into physics. He does not make students perform (unnecessary) calculations, but lets them use their physics intuition.

Thus not only do the lectures contribute to students’ insight into physics, but also to their enjoyment of the subject. Students are particularly appreciative of the fact that Tjerk makes it possible in the concluding practical, ‘Signal Processing and Noise’, to perform assignments with his research group. In this way, even before the Bachelor’s research, students can gain experience in conducting research in a scientific environment.

Prof.dr. Peter Stevenhagen Mathematical Institute Nominated for course(s): BSc Algebra 1, A ­ lgebra 2 & Algebra 3 Thanks to his compact but clear dictates which cover the most important algebraic concepts, students are able to grasp the various aspects of algebra in a very short time.

All dictates are available online in Dutch and in other languages so that students become familiar with the English, German and French terminology. During lectures, students are challenged to make their own connections. Characteristic for Peter’s lectures are the so-called ‘democratic mathematics’, where a difficult question is posed and the audience may vote on the answer, and the ‘homework system’. In the ‘homework system’ assignment points differ in weight depending on the degree of difficulty. Students may choose what assignments they will do. With this method students wanting to achieve high marks are stimulated to do their utmost best.

Additionally, Peter devotes considerable time to the practical applications of algebra, and the application of algebra in other fields.

Dr. Walter Kosters Leiden Institute of Advanced Computer Science Nominated for course(s): BSc Programming Methods

Dr. Sylvestre Bonnet Leiden Institute of Chemistry Nominated for course(s): MSc Metals and Life, MSc Photo­ chemistry

In teaching programming methods, Walter Kosters deals with first-year students in four disciplines: Physics, Astronomy, Mathematics and Information Technology. Despite the large numbers of students, every year afresh Walter succeeds in imparting the principals of programming to a significant number of first-years. Walter also teaches the second-year subject, ‘Artificial Intelligence’. This subject is known for its whimsical and challenging practical assignments, and is much-favoured among many students for this reason.

Nominated for course(s): MSc Metals and Life, MSc Photochemistry At the end of 2009 Dr Bonnet began as Assistant Professor at the Institute for Chemistry, the Biomimetics & Inorganic Materials group. Since then he has played an increasingly important role within the institute. Sylvestre is known as a dedicated teacher who is also prepared to do that little bit extra for students, outside lecture times as well. His Metals and Life and Photochemistry lectures are always rated excellent. Alongside teaching, Sylvestre also devotes himself to research, having acquired a VIDI grant and an ERC Starting Grant.

Prof.dr. Gijs van der Marel Leiden Institute of Chemistry Nominated for course(s): BSc Organic Chemistry 1 Prof. G. van der Marel, or simply Gijs, masters the art of communicating Organic Chemistry in such a way that students will (however briefly) believe it to be the world’s finest subject. In the eyes of the students Gijs is the image of what you imagine an organic chemist to be: a slightly confused demeanour, somewhat chaotic and bristling with humour. Despite the chaos Gijs has a clear structure in his lectures, and he is always prepared to give extra explanation, during working lectures as well.

His explanations are clear, and students know what is expected of them. Nevertheless students don’t have an easy ride with Gijs.

They are encouraged to work hard. In subject appraisals the disciplines Gijs conducts always score high, or maximum.

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Dr. Maarten de Smit Leiden Institute of Chemistry Nominated for course(s): BSc Life Science & Technology Practical Gen technology and Biochemis­ try, BSc Bio Pharmaceutical ­Sciences Practical Biochemistry 1.

Dr. Miranda van Eck Leiden Academic Centre for Drug Research Director of Education Nominated for course(s): Minor Modern Drug Discovery, BSc ‘Theme Drug Delivery – and Targeting’

Dr. Marcel Schaaf Institute of Biology Leiden Nominated for course(s): his contribution in multiple BSc and MSc courses, especially the BSc course Cell Biology and BSc Imaging Techniques

Maarten is the coordinator of the Gene Technology and Biochemistry 1 practical for the Life Science & Technology programme, and the Biochemistry practical for the Bio-Pharmaceutical Sciences programme. Maarten is noted for his unrestrained dedication to the two practicals. Both practicals are among the most challenging of the academic year and are vitally important for the students: you learn new skills and how to apply the knowledge learned during lectures. Here Maarten concentrates on quality, he checks most of the reports himself, and he measures them against a strict yardstick to ensure that they meet the standards. Contact with the students is also important; for this reason Maarten can often be found in the lab, and at least once a day he visits all the labs.

The teaching and structure of a programme plays a vital role during the start and passage of each academic period. Miranda van Eck bears joint responsibility for both aspects, both as a teacher and in her role as director of Education. Every BSc and MSc student will deal with Miranda at some stage during their ­studies.

With her wide knowledge she stimulates students to think about their place in the current medicine era and the possibilities and opportunities in the future. ‘How can a graduate contribute to improving and above all, reformulating medicine development?’ Miranda is open to advice and criticism and is an accessible staff-member: a highly involved and dedicated teacher and director of education who has her heart in the discipline. She does everything possible to give every student the start needed for a splendid career.

Marcel is involved in a number of courses for both Bachelors’ and Masters’ programmes. His courses focus mainly on Cell Biology and the resources and techniques used in the discipline. In his lectures he often uses examples from his own research.

The Imaging Techniques course Marcel delivers in the second year is one of the most difficult of that academic year. The course is mainly about microscopy and the use and operation of various types of microscope. Thanks to his wide knowledge and method of presentation and explanation, the subject is interesting to follow.

It’s hardly surprising that the subject is always judged well during ­appraisals. In addition to good ­teaching, Marcel is also well-liked by students because he is always there for them and tries to introduce improvements where needed.

Awards and Prices in 2013 education

BSc Molecular Sciences Computer Science and Mathematics MSc Astronomy MSc Bio-Pharmaceutical Sciences MSc Bio-Pharmaceutical Sciences MSc Bio-Pharmaceutical Sciences MSc Chemistry MSc Industrial Ecology MSc Mathematics MSc Media Technology MSc Physics MSc Science Based Business

Prices and Honours

Tshego Epema, Myrthe Crombaghs and Joost Nijskens received a Topsector Chemistry Fellowship from the Association of the Dutch Chemical Industry (VNCI) Team 'Geen Syntax' (no Syntax) consisting of Bas Nieuwenhuizen, Mathijs van de Nes and Raymond van Bommel won the Benelux Algorithm Programming Contest 2013 Marijke Segers won the Lorentz Graduation Prize from the Royal Holland Society of Sciences Marjolein Soethoudt won the Unilever Research Prize 2013 Lisa van Weert received the KNMP student prize from the Royal Dutch Association for the Advencement of Pharmacy Tijmen Booij received the Suzanne Hovinga Award for best internship at the Leiden Academic Centre for Drug Research from the Suzanne Hovinga Foundation Rik Mom won the AkzoNobel Graduation Prize for Chemistry Proces technology from the Royal Holland Society of Science Kirstine Schniebel and Pietro Galgani were awarded with the Stans Prize 2012 Stephanie van der Pas received the ASML Graduation Prize for Mathematics from the Royal Holland Society of Sciences (KHMW) Lieven van Velthoven won the 2nd place in Future Ideas European Master Thesis competition Jelmer Wagenaar won the Shell Graduation Prize for experimental Physics from the Royal Holland Society of Sciences (KHMW) Ingmar van Hengel, Paul Ormel, Tessa Sandberg and Eline Kuiper won the Digital Award from the Philips Innovation Awards with their project Skinprint

Other

BSc Biology and BSc Astronomy receive Top Rating predicate from the national 'Guide to Universities' (Keuzegids Universiteiten) The Leiden University student team consisting of Niels Brouwer, Willemijn van Mossevelde, Daan Jacobs, Mike Spaans and Jonathan Barnhoorn won the 'De grote Willem Quiz' from the television show 'De Wereld Draait Door' in a battle against students from the University of Amsterdam. The Quiz was broadcasted as a special edition of the famous Dutch television show at the night before the coronation and was inspired by the BBC show 'University Challenge'

Science Campus

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Building for the future

The construction of the new Science Campus - in Dutch the Bèta Campus - has been festively launched on February 28, 2013. Because of the length and the size of the project, building activities are divided into three phases. The first phase of the Science Campus should be ready by the end of 2015, the second in 2019 and third in 2022. Most of the existing buildings will ­disappear, except for the famous landmark of the Faculty of ­Science, the quirky designed ‘dish’, which will be ­completely renovated.

between the axis and the laboratories and offices, a transparent wall is added at the corridors side. A parking facility for bicycles, motorcycles and 500 cars, will be realized underneath the complex.

The Science Campus will be durably constructed according to the criteria of the international standard for sustainable construction BREEAM. The construction of the first phase will take two years and is set to be ready for use in 2016.

The new Science Campus will offer a new environment to the realization of our research and education goals at the international level. An important element in the five-storey building is the so-called central axis: a long corridor that runs from front to back of the complex equipped with walkways both in length and width. The axis will serve as a meeting place and enables staff and students to connect. In order to establish a connection

During the fes­ tive launch of the start of the building activities, the dean of the Faculty of Science received the international BREEAM certificate of the Dutch Green Buil­ ding Council. The BREEAM certificate is a renowned label for sustainable construction. An extraordinary achievement: it was the first time a building with laboratory received the certificate.

Progress and activities regarding to the building of our Science Campus can be followed via our (Dutch) website which also provides a live connection from the construction site and a virtual model of the complex. You can also follow the Science Campus via Facebook and Twitter.

BetaCampusFWN, Beta Campus FWN www.science.leidenuniv.nl/index.php/betacampusfwn

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Our science community 21 | 11 m

24 | 10

Staff members Faculty of Science* Total

1946 1321 67.9% 625 32.1% Male

Female

* Ultimo 2013, including guest and honorary staff

15 | 5

f

870 | 368

44 | 23

15 | 12 8 |5 10 | 14

40 | 20

39

12 | 1

6|7

8|6

67 | 44 7|3

10 | 10 9|2

20 | 6

Dutch vs other nationalities Dutch

80 8 | 13

Nationalities

63.6% 1238 36.4% 708

Other nationalities

Faculty of Science Postbus 9502 2300 RA Leiden 071 527 69 90 Fax: 071 527 69 97 science.leidenuniv.nl

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