Cambridge Stem Cell News Issue 15

Cambridge Stem Cell News can be downloaded at:

www.stemcells.cam.ac.uk

Issue 15 - Autumn/Winter 2018

CAMBRIDGE ST E M C E L L NEWS

Transforming Lives through Stem Cell Research

In this issue: Institute updates • • • • •

New Affiliate Group Leaders Stem Cell Research Awards European Awards UKRMP 4DCellFate Project Film

Recent events • Cambridge International Stem Cell Symposium • Cambridge Organoid Meeting • Infinite Potentials Exhibition • Fundraising for NAITbabies • European Researchers Night

Research highlights • Family tree of blood production reveals hundreds of thousands of stem cells • Genetics allows personalised disease predictions for chronic blood cancers • New insights into the role of the NuRD Complex in gene expression • Potential target for lung cancer treatment discovered

Recent Publications Interview • 15 mins with...

Dr Agata Kurowski

Prof Tony Green Institute Director It has been an exciting six months for the Cambridge Stem Cell Institute.

Alongside the final preparations for our move to the Capella building, now formally named the Jeffrey Cheah Biomedical Centre, there has been much activity on multiple fronts, as well as notable achievements for Institute and Affiliate PIs. George Vassiliou and Ewa Paluch were successful in their ERC consolidator awards; Anna Philpott received the Anne McLaren award from the International Society of Differentiation recognising outstanding women in developmental biology; and Meritxell Huch was awarded the Dame Sheila Sherlock Research Prize which recognises outstanding young researchers shaping the field of hepatology. Congratulations to you all on these excellent achievements.

September saw our “inaugural” International Stem Cell Symposium which brought together stem cell researchers spanning multiple fields. Almost 500 delegates joined us for three highly enjoyable days of scientific talks, poster presentations and networking at West Road Concert Hall. Thank you to all those who made this such a vibrant and successful event.

The Public Engagement team continue to develop new and innovative ways to engage ‘harder to reach’ audiences that may have little or no contact with science and research. One such activity was “Infinite Potentials”, an ambitious International Stem Cell Art Exhibition co-curated by the Institute and the SciArt Center in New York. As well as public visitors, this event also caught the attention of Cambridge local MP Daniel Zeichner, who joined me for a tour of the exhibition in June. More details on this and other public engagement activities can be found in the following pages.

As a hub of the University’s Stem Cell Interdisciplinary Research Centre, the Institute continues to facilitate collaborative, cross-disciplinary engagement across the wider stem cell community in Cambridge. As an example, the first Cambridge Organoid Meeting was held in July, bringing together scientists from a range of backgrounds to share their latest research in this field. The event was an excellent forum for knowledge exchange and captured the spirit of collaboration we have here in Cambridge. Watch this space for more interdisciplinary workshops and other events in 2019.

The Wellcome - MRC Cambridge Stem Cell Institute is a world-leading centre for stem cell research with a mission to transform human health through a deep understanding of stem cell biology. Bringing together biological, clinical and physical scientists, the Institute explores and defines the properties of stem cells to establish their true medical potential. www.stemcells.cam.ac.uk SENIOR AWARDS & PRIZES

@SCICambridge

Institute Updates New affiliate Group Leaders Since the Summer, the Institute has appointed three new Affiliate Principal Investigators: Sarah Bray, Professor of Developmental Biology and Ewa Paluch, Professor of Anatomy, both in the Department of Physiology, Development and Neuroscience; and Paul Lehner, Professor of Immunology and Medicine in the Department of Medicine.

Institute affiliates are independent group leaders whose research intersects with stem cell biology and medicine. We now have an excellent group of 34 affiliate researchers spanning 12 Departments (across 3 Schools), as well as the Gurdon Institute, Wellcome Sanger Institute, Babraham Institute and Microsoft Research.

More about our affiliates here: www.stemcells.cam.ac.uk/research/affiliates

STEM CELL RESEARCH AWARDS Dr Meritxell Huch In September, Institute affiliate researcher Dr Meritxell Huch received the Dame Sheila Sherlock Research Prize, a major award from the British Association for the Study of the Liver to recognise young researchers who are shaping the future of UK Hepatology.

This prize is awarded annually to recognise the enormous contribution of Dame Sheila Sherlock to the development of Hepatology as a discipline in its own right.

Prof anna philpott Also in September, Prof Anna Philpott received the Anne McLaren award from the International Society of Differentiation.

Prof Philpott presented a prize plenary lecture at the ComBio conference, a major biennial event for life science researchers in Australia and New Zealand, that was held jointly with the International Society of Differentiation in Sydney, Australia.

This award is presented to women in recognition of both their outstanding scientific contribution to the advancement of the field of cell and developmental biology, and for being an inspirational role model for upcoming young scientists.

European grants awarded to dr George Vassiliou and Prof Ewa paluch

Dr George Vassiliou and Prof Ewa Paluch were recently successful in securing prestigious European Research Council funding. Dr Vassiliou will study how genetic mutations involved in RNA splicing can start a process that leads to the development of lethal blood cancers, such as the myelodysplastic syndromes and acute myeloid leukaemia. Prof Paluch will investigate the molecular control of actin network architecture and mechanics during cell shape changes.

The European Research Council, set up by the European Union in 2007, is the premiere European funding organisation for excellent frontier research. Grants are awarded to outstanding researchers of any nationality who have an excellent scientific track record that shows great promise. To date, the European Research Council has funded some 9,000 top researchers at various stages of their careers, and over 50,000 postdocs, PhD students and other staff working in their research teams.

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CAMBRIDGE SCIENTISTS ARE A HUB OF UK WIDE RESEARCH EXCELLENCE IN REGENERATIVE MEDICINE Earlier this year, Prof Roger Barker and a team based across three UK universities received £5,000,000 in new Government funding to continue their important interdisciplinary research which aims to bring human pluripotent stem cell therapies to the clinic.

Human pluripotent stem cells and regenerative medicine hold significant promise for a range of diseases, such as Parkinson’s disease, liver disease and macular degeneration. “In this new research hub we are looking to develop key platforms that will enable the translation of any pluripotent stem cell-derived therapy for clinical use,” explained Prof Barker.

The Cambridge team and their collaborators at the University of Sheffield, Loughborough University and the Babraham Institute in Cambridge are one of three complementary research hubs which make up the wider UK Regenerative Medicine Platform (UKRMP).

UKRMP is funded by the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC), and brings together the brightest minds in regenerative medicine from across 16 different UK universities and institutions.

Find out more here: www.ukrmp.org.uk

European stem cell research captured on film The Cambridge scientists at the heart of a collaborative European stem cell project feature in a new short film which captures the key outputs of their five year 4DCellFate project.

The 4DCellFate project brought together 12 different Institutes from 8 countries to share expertise and investigate how cells develop from a single cell to a functioning body with almost 200 different cell types.

The film includes interviews from the project coordinator Prof Luciano Di Croce (Center for Genomic Regulation, Barcelona) and the two lead Cambridge researchers Prof Ernest Laue and Dr Brian Hendrich, as well as animations to explain the scientific background.

The 4DCellFate project studies two important protein complexes involved in the control of cell fate, PRC and NuRD. As well as analysing the detailed structure and function of these protein complexes, the roles of PRC and NuRD in diseases such as Leukaemia were also investigated.

Watch the film in full here: www.youtube.com/watch?v=FD60-3XEeVs&t=168s

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Recent Events & Activities 6th Cambridge International stem cell symposium In September, members of the global stem cell community arrived in Cambridge to take part in the three-day International Stem Cell Symposium. Over 450 delegates gathered at West Road Concert Hall to hear talks from leading stem cell scientists and share their own research with collaborators and friends from around the world.

The event officially began with opening addresses from Prof Chris Abell, Pro-Vice Chancellor for Research, and Prof Patrick Maxwell, Head of the School of Clinical Medicine. The programme followed with a range of excellent talks across a broad spectrum of topics, including: the fundamental biology of stem cell development; the physical role of the stem cell environment in brain ageing; the use of stem cells in the production of platelets for human transfusion; and a number of presentations examining the future applications of stem cell research for therapeutic intervention for diseases such as cancer, liver disease and Parkinson’s disease.

One particular highlight was the Topical Debate, which addressed the motion that “Stem cell therapies will never be curative for adult onset degenerative conditions”. Prof Roger Barker argued eloquently in support of the motion and Prof Malin Parmar proposed compelling opposing arguments. After an excellent floor discussion the audience voted against the motion, concluding there is a bright future ahead for stem cell therapies.

Students and Post-doctoral researchers showcased their science during poster sessions on Wednesday and Thursday evening, with selected individuals challenged with presenting their research projects to the conference in a ninety second ‘elevator pitch’.

A judging panel then selected the best posters and pitches with prizes generously supplied by headline sponsor STEMCELL Technologies. The winning poster pitch was Caroline Busch, PhD Student from the University of Glasgow, and the two best posters were Patrick Fortuna, PhD Student from the University of Queensland, and Thierry Jarde, Post-doc from Monash University.

In addition to the poster sessions, delegates had time to meet and interact more informally during the Gala Dinner at the impressive Trinity College. Under the watchful eye of Henry VIII, students, post-docs and PIs shared research stories and anecdotes, as well as email addresses as new collaborations and research partnerships formed.

Find out more here: www.stemcells.cam.ac.uk/events/symposium2018

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Cambridge is shaping the future of organoid research Organoids, or ‘miniature organs’, are a rapidly growing area of stem cell research, with far reaching implications for personalised and regenerative medicine. Cambridge has a wealth of organoid expertise, with scientific specialisms including miniature livers, wombs, lungs and brains.

In the spirit of greater knowledge sharing and collaboration in the organoid field, July saw the first Cambridge Organoid Meeting, bringing together fifty interdisciplinary researchers from across the University of Cambridge, as well as scientists from the Wellcome Sanger Institute, MRC Laboratory for Molecular Biology, Gurdon Institute, Cambridge Cancer Centre and the Wellcome – MRC Cambridge Stem Cell Institute.

Prof Alfonso Martinez-Arias, who took the scientific lead on the meeting, said “The event was a great success, it was very useful to hear about the wide range of Organoid research going on across Cambridge. Getting everyone together to share research findings and ideas in a collaborative way is so important to advance our understanding. I really feel that Cambridge is in a great position to shape the future of organoid research”.

Read more about the Organoid research going on across Cambridge here: www.cam.ac.uk/bodyinminiature

stem cell International Seminar series The Institute’s International Seminar series has continued to attract prominent speakers from around the world, spanning a broad range of disciplines and showcasing basic research through to bedside applications.

Over the summer, the Institute hosted Prof Lorenz Studer, from Memorial Sloan Kettering Cancer Center, USA, who spoke on “Modelling and treating neural disease using human pluripotent stem cells”, as well as Prof Jonas Frisén (Karolinska Institute, Sweden) who gave a talk titled “New cells in old brains”.

Prof Connie Eaves from the Terry Fox Laboratory, Vancouver, spoke in September about “Hematopoiesis 2018”, and the final talk of 2018 was from Prof Christine Mummery (Leiden University, Netherlands), on “Human pluripotent stem cells in cardiovascular disease: where are we now?”

We look forward to hearing more about ground breaking stem cell research in 2019.

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International stem cell art exhibition unveiled in Cambridge and New York To explore the future of stem cell research from an artistic perspective, the Wellcome – MRC Cambridge Stem Cell Institute and the SciArt Center (New York) launched a new international exhibition entitled “Infinite Potentials”.

Artists from around the world were asked to respond to the question “If stem cells were the artistic medium by which we design our future, what does the future look like?” 127 submissions were received from the international artistic community, including artists in Israel, France and the USA.

A group of researchers at the Institute and the SciArt Center curatorial team reviewed the submissions and selected 38 pieces that best captured the future possibilities of stem cell research and therapeutic opportunities.

During the MRC Festival of Medical Research in June, we hosted Daniel Zeichner, the MP for Cambridge, at the exhibition. Daniel was shown the artworks by Institute Director Prof Tony Green and had the chance to meet some of the researchers and local artists who participated in the project.

Jamie McGinn, a stem cell scientist involved in the selection of the artwork said “I was excited to be involved in this art – science collaboration as part of the Cambridge Stem Cell Institute’s public engagement programme. It was amazing how different each piece of art was, and interesting to see how artists from around the world interpret stem cell biology and the potential of these cells to shape the future of human health”.

Dr Jamie Dorey, Institute Public Engagement Manager said “The blending of art and science within this exhibition has given us insight into how those outside of academia view stem cell research while also providing an accessible route to engage and inspire a diverse international audience. We are excited to explore future opportunities to work with the SciArt Centre and other organisations on high quality, high-impact public engagement projects.”

After the Cambridge leg, the full 38-piece exhibit moved on to the New York Hall of Science, where it will be on display until January 2019.

Read more here: www.sciartcenter.org

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newmarket all in to raise funds for naitbabies In October, group leader Dr Cédric Ghevaert hosted a charity concert to raise funds and awareness of NAITbabies, a support group for women affected by neonatal alloimmune thrombocytopenia (NAIT).

Dr Ghevaert’s research investigates blood stem cells, including how platelets are produced in the body. NAIT is a disease caused when a mother and child have incompatible platelets and affects 1 in 1000 pregnancies. In severe cases, NAIT leads to a low platelet count which puts the baby at risk of dangerous bleeding, sometimes leading to disability or death.

The event was full of music, performing arts and poetry, including one of the UK’s leading concert organists Anne Page, Italian tenor Alessandro Cortello, and Stagecoach Newmarket. Dr Ghevaert himself played the organ alongside his family. The event was very well attended and raised around £1000 for the charity!

Stem cell research on show in Cambridge and Peterborough On a weekend in September, researchers from the Cambridge Stem Cell Institute took part in LifeLab, as part of European Researchers Night, the largest public science event in Europe.

Led by the Wellcome Genome Campus, LifeLab aims to bring cutting edge research to communities with limited access to science through a range of talks, hands on activities and other forms of engagement. Our Institute research was well represented across the event, taking part in activities in Peterborough and Cambridge.

Institute researchers: Michelle Wantoch, Thorsten Klampfl, Daniel Prins, Juliet Aungier and Changzhu Fu were out in Cathedral Square, Peterborough, talking to people about blood stem cells and running our much-loved stem cell robots activity.

Elsewhere, Prof Ludovic Vallier and Julia Spindel talked about their research over pizza and Regenerator beer with audiences at the Cambridge Science Centre.

Across two days, over 3,500 members of the public in Cambridge and Peterborough engaged with stem cell research. LifeLab will return on Friday 27 and Saturday 28 September 2019.

Find out more here: www.cam.ac.uk/news/cambridge-life-lab-project-wins-place-in-europes-largest-public-science-event 8| Cambridge Stem Cell News

Research Highlights Family tree of blood production reveals hundreds of thousands of stem cells Adult humans have many more blood-creating stem cells in their bone marrow than previously thought, ranging between 50,000 and 200,000 stem cells. Researchers from the Wellcome Sanger Institute and Wellcome – MRC Cambridge Stem Cell Institute developed a new approach for studying stem cells, based on methods used in ecology.

The results, published in Nature, present a new opportunity for studying, in humans, how stem cells throughout the body change during ageing and disease. Using whole genome sequencing to build and analyse a family tree of cells, this work could lead to insights into how cancers develop and why some stem cell therapies are more effective than others.

All of the organs in our body rely on stem cells in order to maintain their function. Adult stem cells found in tissues or organs are a self-sustaining population of cells whose offspring make all of the specialised cell types within a tissue.

Blood stem cells drive the production of blood, and are used in treatments and therapies such as bone marrow transplantations – a treatment for leukaemia that replaces cancerous blood cells with healthy blood stem cells.

However, blood stem cells in humans are not fully understood, with even some of the most basic questions, such as how many cells there are and how they change with age, not yet answered.

For the first time, scientists have been able to determine how many blood stem cells are actively contributing in a healthy human. Researchers adapted a method traditionally used in ecology for tracking population size to estimate that a healthy adult has between 50,000 and 200,000 stem cells contributing to their blood cells at any one time.

Scientists found the number of stem cells in the blood increases rapidly through childhood and reaches a plateau by adolescence. The number of stem cells stays relatively constant throughout adulthood.

Dr David Kent, a joint senior author from the Wellcome-MRC Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, said: “This new approach is hugely flexible. Not only can we measure how many stem cells exist, we can also see how related they are to each other and what types of blood cells they produce.

Image credit: Mairi Shepherd (Kent Lab)

Applying this technique to samples from patients with blood cancers, we should now be able to learn how single cells outcompete normal cells to expand their numbers and drive a cancer. As the cost of genomic sequencing comes down, it is transforming scientific research such that studies previously thought to be impossibly large, are now becoming routine. It is a very exciting time to be working in this space.”

Reference: Population dynamics of normal human blood inferred from somatic mutations. Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K, Belmonte M, Osborne RJ, Huntly BJP, Martincorena I, Anderson E, O’Neill L, Stratton MR, Laurenti E, Green AR, Kent DG, Campbell PJ is published in Nature, September 2018.

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Genetics allows personalised disease predictions for Chronic blood cancers Scientists have developed a successful method to make truly personalised predictions of future disease outcomes for patients with certain types of chronic blood cancers. The study from the Wellcome Sanger Institute, the WellcomeMRC Cambridge Stem Cell Institute, the University of Cambridge, and their collaborators, combined extensive genetic and clinical information to predict the prognosis for patients with myeloproliferative neoplasms. The research also identified eight different genetic subgroups of the disease that link with patterns of clinical disease and patient prognosis.

This work could lead to personalised medicine for patients with these blood cancers. It will help doctors identify those patients who are likely to have a very good future outlook, and which patients may benefit from specific treatments or clinical trials.

Myeloproliferative neoplasms are a group of blood cancers affecting around 30,000 patients in the UK. These cancers are chronic, long term conditions and patients suffer from a risk of blood clots and bleeding. In addition, these cancers can progress to more advanced forms of disease, including acute leukaemia, that have a poor outlook. It is important to patients to know how their disease is likely to progress in the future, but it has not previously been possible to provide personalised predictions for each individual patient.

Professor Tony Green, a senior author on the paper said: “This work represents a step change in our understanding of the myeloproliferative neoplasms. Not only does it reveal a new classification based on causal mechanisms but it also provides for the first time personally-tailored predictions to guide patient management.”

The study also revealed that some subgroups shared features with other blood cancers. This work could bring clarity to disease classification of blood cancers in the future and enable the development and testing of new treatments.

Reference: Classification and personalised prognosis in myeloproliferative neoplasms. Grinfeld J, Nangalia J, Baxter EJ, Wedge DC, Angelopoulos N, Cantrill R, Godfrey AL, Papaemmanuil E, Gundem G, MacLean C, Cook J, O’Neil L, O’Meara S, Teague JW, Butler AP, Massie CE, Williams N, Nice FL, Andersen CL, Hasselbalch HC, Guglielmelli P, McMullin MF, Vannucchi AM, Harrison CN, Gerstung M, Green AR, Campbell PJ is published in the New England Journal of Medicine, October 2018.

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new insights into the role of NuRD in gene expression The vast majority of cells in the body contain exactly the same set of genetic instructions, however they are able to develop very different characteristics. Cells in the heart, the brain, the liver, or the skin are all genetically identical but adopt different shapes and serve different functions. The cell’s instruction manual is found within the genetic code on the DNA, and the characteristics of a given cell are chosen based on the genes that are turned on or turned off in that cell.

Researchers in Dr Brian Hendrich’s lab at the Cambridge Stem Cell Institute used mouse embryonic stem cells to study a cluster of proteins called “The NuRD Complex”, known to be important for controlling gene expression. While previous work indicated that NuRD simply turns genes off, the researchers found that NuRD’s role in controlling gene expression is actually more subtle; fine tuning the activity of genes rather than acting as an on-off switch.

The group found that NuRD directly controls how sections of DNA, important for controlling gene expression, are packaged within the cell. Changing the DNA packaging affects the access of other regulatory proteins to the genes within the DNA. For example, NuRD controls the access of RNA polymerase, the protein complex which “reads” the genes within the DNA. Importantly, this control of protein access by NuRD does not cause all-or-nothing changes in gene expression as was previously thought, but rather acts to finely regulate genetic activity.

“NuRD acts as something like a gatekeeper, deciding which proteins can access the DNA and therefore which genes are able to respond when a stem cell needs to differentiate into one cell type or another“ explained Dr Nicola Reynolds, one of the lead authors on the study. “Stem cells are particularly sensitive to this since these cells can differentiate into many different cell types. These cells use NuRD’s ability to finely tune gene expression in order to make the right decisions at the right time.”

Dr Hendrich said “This work is important for understanding fundamental biological questions about how stem cells decide which cells to become, but will also guide future work into human diseases, such as cancer, where the cellular decision making processes are disrupted.”

Watch the video animation here: www.stemcells.cam.ac.uk/research/pis/hendrich Reference: The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression. S Bornelöv, N Reynolds, M Xenophontos, S Gharbi, E Johnstone, R Floyd, M Ralser, J Signolet, R Loos, S Dietmann, P Bertone, B Hendrich is published in Molecular Cell, July 2018.

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Potential target for lung cancer treatment discovered Lung squamous cell carcinoma (LUSC) is a type of lung cancer that accounts for more than 400,000 deaths worldwide each year. Cambridge based scientists and their collaborators used mouse and stem cell models to understand the molecular pathways involved in the development of this type of lung cancer and revealed potential new avenues for drug development.

The researchers found that LUSC cells contain high amounts of a protein called BCL11A, and that manipulating the gene responsible for producing this protein stopped the development of LUSC. The scientists also showed that the growth of LUSC cancer cells could be inhibited using drugs targeting the BCL11A protein signalling pathways inside the cells.

Dr Kyren Lazarus, study author from the University of Cambridge, said: “How LUSC develops is a bit of puzzle – until now our molecular understanding of this process was limited. Our research has revealed a major piece of this puzzle, which we are now actively trying to make new drugs against.”

This promising early research has led to further funding being granted by Cancer Research UK to facilitate the development of a drug which could one day lead to a new treatment option for some people with lung cancer.

“Developing targeted treatments is a real opportunity for improving the outlook for patients. With this new drug discovery grant from Cancer Research UK we are working to develop small molecules to specifically block BCL11A in LUSC cells”, explained Dr Walid Khaled, lead author from the University of Cambridge and affiliate researcher with the Cambridge Stem Cell Institute. “We are aiming to disrupt critical interactions that BCL11A has with other proteins and are working closely with our colleagues at the Department of Biochemistry in Cambridge and CRUK Beatson Institute Drug Discovery Unit to achieve this.”

Over the last 40 years, lung cancer survival has remained stubbornly low, particularly when compared to overall cancer survival which has more than doubled. One of the reasons for this is the lack of targeted treatments for lung cancer, and currently just 5 in 100 people survive their disease for 10 or more years.

Professor Karen Vousden, Cancer Research UK’s chief scientist, said: “Identifying potentially druggable targets is an early yet crucial stage in the journey towards precision medicine. While there is much to be done before this work could be translated into patient benefit, it’s a fundamental step towards that goal and we look forward to seeing how this discovery progresses along the research pipeline.”

Reference: BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma. Lazarus KA, Hadi F, Zambon E, Bach K, Santolla MF, Watson JK, Correia LL, Das M, Ugur R, Pensa S, Becker L, Campos LS, Ladds G, Liu P, Evan GI, McCaughan FM, Le Quesne J, Lee JH, Calado D, Khaled WT is published in Nature Communications, August 2018.

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Recent Publications Transcription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision. Dalby A, Ballester-Beltrán J, Lincetto C, Mueller A, Foad N, Evans A, Baye J, Turro E, Moreau T, Tijssen MR, Ghevaert C. Stem Cell Reports. 2018 Dec 11;11(6):1462-1478 Classification and Personalized Prognosis in Myeloproliferative Neoplasms. Grinfeld J, Nangalia J1, Baxter EJ, Wedge DC, Angelopoulos N, Cantrill R, Godfrey AL, Papaemmanuil E, Gundem G, MacLean C, Cook J, O’Neil L, O’Meara S, Teague JW, Butler AP, Massie CE, Williams N, Nice FL, Andersen CL, Hasselbalch HC, Guglielmelli P, McMullin MF, Vannucchi AM, Harrison CN, Gerstung M, Green AR, Campbell PJ. New England Journal of Medicine. 2018 Oct 11;379(15):1416-1430 Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors. Belluschi S, Calderbank EF, Ciaurro V, Pijuan-Sala B, Santoro A, Mende N, Diamanti E, Sham KYC, Wang X, Lau WWY, Jawaid W, Göttgens B, Laurenti E. Nature Communications. 2018 Oct 5;9(1):4100 Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia. Mangolini M, Götte F, Moore A, Ammon T, Oelsner M, Lutzny-Geier G, Klein-Hitpass L, Williamson JC, Lehner PJ, Dürig J, Möllmann M, Rásó-Barnett L, Hughes K, Santoro A, Méndez-Ferrer S, Oostendorp RAJ, Zimber-Strobl U, Peschel C, Hodson DJ, Schmidt-Supprian M, Ringshausen I. Nature Communications. 2018 Sep 21;9(1):3839 Population dynamics of normal human blood inferred from somatic mutations. Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K, Belmonte M, Osborne RJ, Huntly BJP, Martincorena I, Anderson E, O’Neill L, Stratton MR, Laurenti E, Green AR, Kent DG, Campbell PJ. Nature. 2018 Sep;561(7724):473-478 BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma.

Lazarus KA, Hadi F, Zambon E, Bach K, Santolla MF, Watson JK, Correia LL, Das M, Ugur R, Pensa S, Becker L, Campos LS, Ladds G, Liu P, Evan GI, McCaughan FM, Le Quesne J, Lee JH, Calado D, Khaled WT. Nature Communications. 2018 Aug 20;9(1):3327 Prediction of acute myeloid leukaemia risk in healthy individuals. Abelson S, Collord G, Ng SWK,…, Brennan P, Vassiliou GS, Shlush LI. Nature. 2018 Jul;559(7714):400-404 The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression. Bornelöv S, Reynolds N, Xenophontos M, Gharbi S, Johnstone E, Floyd R, Ralser M, Signolet J, Loos R, Dietmann S, Bertone P, Hendrich B. Molecular Cell. 2018 Jul 5;71(1):56-72

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Interview 15 mins with...Dr Agata Kurowski

Dr Agata Kurowski first joined the Cambridge Stem Cell Institute in the summer of 2008 as a part of a project in the lab of Dr Michaela Frye. She then began her PhD under the supervision of Dr Anton Wutz and Prof Jennifer Nichols, which focused on ‘The Establishment and Maintenance of the Pluripotency Network in the Pre-Implantation Mouse Embryo’. In 2016, she moved to New York to begin her postdoctoral career at the Icahn School of Medicine at Mount Sinai.

She is currently working in the laboratory of Dr Martin Walsh in the Department of Pharmacological Sciences. Her research focuses on epigenetic regulators in embryonic stem cells. She also serves as Co-Chair of the Mount Sinai Postdoctoral Association, representing 600 fellow postdocs.

Q1: Why did you choose to do your PhD at the Cambridge Stem Cell Institute?

I always had a passion for developmental biology. As a child, I was fascinated by animal development and devised small experiments, like housing frog eggs and examining their transformation. Later, I became interested in stem cell research as it is a hugely multidimensional field contributing to developments in academic research, as well as the medical industry. My interest in stem cell science was further enhanced during my summer project and masters thesis in the laboratory of Dr Frye. I really enjoyed the atmosphere of the Institute and the University, along with the people who I had the opportunity to work with. This greatly influenced my decision to pursue my PhD at the Cambridge Stem Cell Institute. There are very few institutes in the world with such great international reputation in stem cell research and I knew that it would be the ideal environment to nurture my developing career as a stem cell scientist.

Q2: What is your favourite memory from your time at the Institute?

I have so many great memories from my seven years at the Institute, it is hard to choose just one. The Institute was always a very friendly and social place. I cherish the many people and great scientists I have met over the years, many of which became long lasting friends, even though we are spread all over the world. I look back fondly on the retreats, conferences, and the happy hours, but more importantly the moments when Prof Nichols and I dissected embryos together are the most sentimental. I even treasure the process of writing my PhD thesis at my desk in the Institute. I had the luxury of being next to the coffee machine, which was a quiet place where all the friendly people who were going to make coffee during the day gathered, leading to a lot of controversial conversations, not only about the taste of the coffee!

Q3. How did your time at the Institute prepare you for your future career?

My mentors did a great job in preparing me for the rigors of becoming a professional scientist and a project manager. Attending our regular seminars, stem cell and journal clubs provided me with a broad knowledge on stem cell research. In addition, the Institute offered a huge variety of seminars and conferences to meet with scientists from around the world, and I profit a lot from the network I was able to cultivate while in Cambridge.

Q4. How does life as a researcher in New York, compare to that of a researcher in Cambridge?

In a big city like New York and a large hospital like Mount Sinai, everyone is socially anonymous and professionally autonomous. As a result, it is difficult to get to know the people around you. Due to the college system, and collegial atmosphere that one is afforded in the Institute, it was much easier to build a personal and professional network in Cambridge. In addition, Cambridge distinguishes itself through its history and traditions of the University and the therefore resulting atmosphere that allows one to acclimate and feel at home.

Q5. What advice would you offer to current PhD students at the Institute?

I would advise them to take advantage of all the University and the Institute has to offer. Such as joining the University’s societies, studying extracurricular courses and utilizing the career services available. I would continue by stressing the importance of joining professional networks, in addition to expanding their experience beyond the bench. I believe that by opening their horizons and volunteering for activities outside science will expose them to a lot of opportunities and will benefit their future careers.

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Q6. What excites you most about stem cell research?

With technology rapidly advancing, the last few years have been very exciting. My current research focuses on UHRF1, a protein involved in chromatin and histone modifications. Dr. Walsh recently acquired the lab’s own machine to create single cell libraries. Many protocols, like for ATAC or bisulfite sequencing still need to be developed or optimized, and it is a very exciting process to be a part of. Everything is moving very quickly with the technological enhancements in science and the fact that the understanding of stem cells is leading us to cures of diseases and injuries is extraordinary. The possibility to contribute to stem cell research, which is one of the fastest developing science fields with a bright and exciting future, is extremely stimulating to me.

UHRF1 plays an essential role in propagating DNA methylation patterns during DNA replication through its ability to bind methylated cytosine residues and recruit DNMT1. In contrast to embryonic stem cells, UHRF1 seems excluded in the nuclei and expressed in the cytoplasm of the E3.5 blastocysts, this is unexpected and subject of further investigations.

(Confocal immunofluorescence images. Credit Agata Kurowski.)

Annual institute PhD Day Symposium and away day The Cambridge Stem Cell Institute PhD Day Symposium 2018 was held at the CRUK Cambridge Institute on the Cambridge Biomedical Campus. We had a record attendance number of over 90 delegates throughout the day, including students, postdocs and group leaders from Institute and affiliate research groups.

Delegates heard engaging talks from 13 PhD students soon to begin their final year, plus short talks from three of our event sponsors; STEMCELL Technologies, AstraZeneca and Merck. The event was also supported

by Agilent, Olympus and Microsoft Research, who kindly provided £500 travel grants for the two best talks, which were awarded to Cora Olpe (1st prize, Winton lab) and Blanca Pijuan Sala (2nd prize, Göttgens lab).

Posters were on display in the afternoon from 40 current PhD students from across the Institute. These were judged by a panel of group leaders and senior scientists, who awarded joint first prize to James Che (Kent lab) and Aracely Castillo Venzor (Surani lab).

This year saw the first ‘PhD Student Away Day’ take place the day after the PhD Symposium at the impressive Duxford Imperial War Museum. Organised by Jennifer Jia (Káradóttir lab) and Georgia Stavrou (Zilbaeur lab), the idea was to bring current students together for a day of networking and discussion.

The programme included a workshop on ‘Effective Communication’, a career panel discussion with academics and industry representatives, and a session on ‘Staying in Academia: setting up your own lab’ with Prof Anne Ferguson-Smith, Dr Ana Cvejic, Dr Stephen Montgomery and Dr Emmanuel Derivery. The day concluded with a panel discussion entitled ‘PhD to Enterprise’, with Dr Chibeza Agley, Dr Sean Mac Fhearraigh and Dr Tim Allsopp.

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Front Cover Image: Hematopoietic progenitor cells differentiated in vitro from human pluripotent stem cells.

Credit: Giovanni Canu (Vallier Lab) Back Cover Image: Family tree of blood production reveals hundreds of thousands of stem cells.

Credit: Kent lab