UCD Conway Focus Summer 2014

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Issue 22,23 3 Summer 2014

" A4 new look at the solid-liquid interface things happen 1 !at interfaces Interesting % solids and where meet liquids is no

5 6

exception. Understanding the complex taking at phenomena place the ‘solid(67 -! ! liquid’ interface could give important clues ! 8 ! about how to build better medical 5 batteries,

devices and longer-lasting $ '

but to date it has been difficult to get a !

7 handle on how chemical ions in solution 1

9 behave at this crucial juncture. Until now, 4

: (9 4 :- that is.

% ! 5 6

$

A team led by UCD scientists has developed

tool a new to build up a clearer picture on of what is going at this interface, and can " crucially, do this on the ! nanoscale. The

# procedure, published in Nature $

stands " to enable % Communications, research & and " in biological materials science. $ " % interface is the location “The solid-liquid

of many important physical, biological and ' (" ) " chemical explains , researcher processes,� *+ Liam Collins, who is completing a Ph.D.

- in the " Nanoscale Function Group. “If you . $ want to understand diseases

" " " %biosystems, .

" and novel biomaterials or processes in energy systems like batteries, you need to % what happens at the solid-liquid understand interface.�

/" # " -+ + % " +% "

" on the What happens atomic " level at this

" at interface can have an impact a more

way visible or macroscopic level - the the or " body functions, how quickly a battery

%- so techniques that drains, for example

can operate on atomic-length scales can . " " " improve our fundamental understanding of materials and devices, notes Collins, "

who works with Conway Fellow, Dr Brian

% . Rodriguez. *01., % ' " Existing techniques, such as the atomic

force microscope, already allow researchers " to " get a good ‘view’ of physical

structures " interface at the solid-liquid but not how " 01.% he explains: ions behave at this interface, “So we set out to join structural informa-

- 23 tion with electrochemical function.� " " To get this multi-modal " view, Collins

" worked with colleagues in UCD, $% 4 Oak

" Ridge National USA and Taras Laboratory, " Shevchenko Kiev National " University, Ukraine to develop technique "

called a " electrochemical force microscopy (EcFM).

% 0 of "

is that it The benefit the new technique

" to " allows " " researchers get a clearer picture $ " of what is going on at this key solid-liquid interface in situ rather than making

" " "

$ "

to measurements in air and extrapolating % liquids, explains Collins.The team are now turning their attention to new materials, ' (" one being a form of ultra-thin carbon called " graphene, which applications in energy "

has " storage. the immediate “Probably " improvement this EcFM technique / coming 5 " out of' ' will be better understanding systems a of energy such as double-layer capacitors " and lithium ion batteries,� says “If we can " " Collins. understand the processes on the nanoscale % here, it will in turn allow us to improve the & 6. efficiency and lifetime of devices.� (" " " " ! " He also has an eye to a wide range of longer-term applications that could come " from better understanding the relationship 5 " %7

between structure and function in biologi cal systems. “That may help us to develop " " in vivo batteries that harness biofuels, or to 8 understand like Alzheimer’s + diseases % + & 9 : disease, 0 : . . 1 1 at a : fundamental level.� + + : . : : ' (" ;% + ' % 23 3 / 22<

==*>,?@A >@ (In conversation with journalist, Claire O’Connell for UCD Science showcase)

Reference Collins L et al. Probing charge screening dynamics and electrochemical processes at the solid–liquid interface with electrochemical force microscopy. Nature Communications| 5:3871| DOI:10.1038/ ncomms4871.

Director’s Message ) / Welcome!

1

8 8

Under the latest round of the Science

; Foundation Ireland Investigator Programme, seven research projects led by " UCD and one partnered with Teagasc will " receive funding. This is the joint highest $ number of research projects from any one " (" funding institution to receive under this " $ will be round and five

of these projects led by Conway Fellows. % Congratulations

. to them and the many other Fellows " B to ' ' =3 ;- 23 ;- " A " %

who " continue to secure funding in an 4 C increasingly competitive and challenging " environment. < I was delighted to welcome UCD President, / " Professor Andrew to the " " Deeks " Institute " at the beginning of May and Conway

for

Fellows to have the opportunity

" to " highlight % their contributions to research

Congratulations to " Conway researchers / and alumni who have been actively 0 23 3% organising and participating in science engagements activities such as Pint of 0 " Science, Soapbox Science, and Engage. " " Your passion for research and willingness " peers to reach audiences outside of your

" + will help to embed science firmly within society.

scholarship in the University. 4 -+ $ " " "

Professor Walter " Kolch Director "

%

excellence, innovation and outstanding

"

B 4 : -+ + 0 "

<2:4 <7' ' ' 1 '0 / D;+-D E '0 /; 0+ D ; ; +&

+ 0 . 0

Enabling research and innovation projects 5 5

5 ! 7 9

5 Five research projects led by Conway

4 Fellows in areas of key priority for ' funding : Ireland have secured under the Science Foundation Ireland (SFI) : $ ' 7A ! Investigator programme recently

5 ! announced Richard Bruton

! by Ministers

and Sean Sherlock. Funding for' each 1 ! 9 project ranges from â‚Ź860,000 to â‚Ź1.9 7 1

million over a three to 5 5 five year period. B00"$

Prof Seamas Donnelly will tackle the . 0 . of Pseudomonas treatment aeruginosa is common in patients B infection that % with cystic fibrosis. During infection, .

"

Pseudomonas clump together to form sticky aggregates that develop into a D; N B N biofilm, making them more to " difficult treat with "

" antibiotics.

" “This funding award will allow us to

%

develop new therapies to prevent biofilm . inB . formation patients and make the

easier to bacteria responsible treat with "

to antibiotics. We also hope develop a test that identify those patients will *0' ,

most likely to respond best to this new treatment�, said Prof Donnelly. .

" (" ! " " Prof Ken Wolfe will investigate the sexual D; O B %

reproduction cycles of three yeast species

+ B . of economic importance. Pachysolen 64 is bioethanol + " tannophilus a potential producer - this valuable fuel natural " source also has in the "

" cosmetic % uses and other manufacturing

23 3 industries. " Hansenula polymorpha and Pichia pastoris "

are widely used in the biotechnology industry to express recombinant proteins such as pharmaceuticals.

" " "

" The project will characterise how these undergo mating-type " switching. %7 species This is a natural process in which a yeast + changes . ‘gender’

cell or switches and, as a + " 6.

that . switched cell, it can mate with a cell

has not switched. " "

% . of “When we understand the mechanism be modify switching, we should able to

" the genomes to prevent switching

This will from happening. open up the possibility of using powerful methods of % .

" genetic analysis to improve the production 10 " characteristics of these " industrial yeasts with consequent benefits�,

economic %7 explained Prof Wolfe. . ) B

"

" a Prof Mark Crowe is undertaking " " collaborative project with Prof Michael Diskin from

Teagasc to develop early non

# " invasive and reliable molecular biomarkers 5 B

of pregnancy cattle. Reproductive G in dairy performance in dairy cattle is an "

important factor production affecting # % and economic efficiency particularly in / grass-based A 333 0 as in seasonal systems such Ireland. 0' % +" "

“We intend to

improve

on current commercial methods pregnancy " of detection by . producing reliable " early % a " pregnancy that " can diagnose 00test

" (" within 21 days artificial "

insemination. of " " This would a major advance in the

"

be

%

Patrick

" Lonergan % 0 Prof has been awarded 0' funding to reduce embryo mortality

" " " "

through improved understanding of % . maternal -+ + " embryo communication. Prof Stefan Oscarson 0' intends

to design, " and $ synthesise develop carbohydrate– based vaccines, therapeutics, diagnostics, and medical devices. % 64 for " " 0' Commercialisation award novel " technology $ % . " Dr David O’Connell has patented a tag

technology providing a novel affinity

7 $ B platform for the development of a suite . % 6 " applications for of reagents and product the biotechnology He received $ industry. B " funding under the Enterprise Ireland 7%

Commercialisation Fund 2014 to support

0 " " the development and optimisation of a 00 " protein purification kit. B D; N " the establishment The $ fund will support * / 5, " of a $ start-up company, BlackLabBio, to commercialise this product and subsequent products incorporating the "

%

patented technology. The product will provide significant benefits of enhanced speed, simplicity and performance by reducing process steps involved in protein purification and biosensor display.

reproductive management of dairy herds as current limits between - detection are

days 28 -30 of pregnancy�, explained Prof Crowe.

' &0F "

Recognising excellence A

In recognition his outstanding 1 ! of 9 7 contribution chemistry, Prof Pat to Guiry has been awarded Boyle 5 the % Higgins Medal by the Institute @ > ,Gold

of Chemistry in Ireland. The 5 5 award involves a gold medal and a monetary 5 $ sum to cover expenses for a lecture. &0F

Conway who was Fellow, "Prof Guiry, Institute director from 0 %2004-2005, focuses developing new catalysts on + C

" and synthetic to prepare

methodologies 0 compounds 3 of biological % interest, particularly those with anti-inflammatory properties. " " *D.GB,

PhD student, Liam Collins (Rodriguez 0 % . group) a graduate student received gold award 2014 Materials at the

" Research $ %

" " " "

" "

Society (MRS) Meeting San Spring in

Francisco. recognises graduate This award % students whose academic achievements & and current" materials science research a excellence display high level of and distinction. Liam " recently " published

research Nature Communications. in " % .

B" "

PhD O’Gorman student, Aoife " (Brennan group) won an award the best $ for early career oral " presentation the at 2014 Analytical Tools for Cutting-edge % Metabolomics conference; a joint meeting the Analytical of of Division $ the Royal Society and the D.GB of Chemistry International Metabolomics Society held ("

% in4 London. Aoife recently published (" in the Journal Chromatography B. of " "

"

" $ %

. " " " "

&0F % B " " % 6 " ("

#" "

" " " 7 % . " " 1 " 0 - + " %

Patrick Hobbs (l), President of the Institute of Chemistry ? of Ireland presents Prof Pat Guiry with the Boyle-Higgins / Gold Medal &0F % B" / (" +% % " F 23 3 >CC >A

New guide to data interpretation strategies transform or "

;- 1BK Normalisation manipulate data to allow quantitative

Western blotting is a widely used technique to detect specific proteins. Although considered a semi-quantitative method, the results are often interpreted quantitatively. Scientific articles $ ' often do not specify how researchers quantified A A 9 A their results and how they compared replicates â‚Ź"E+!+00 biological for statistical 5 7 testing. < F

Conway Fellow, Prof Kholodenko and Boris ' (7 F his team in Systems Ireland Biology 5 have 19. described how results of statistical testing 5 $ applied to western blot data are affected by the choice of normalisation strategy applied * % : % ", to the data. They have created a step-by " " "

step guide to help scientists choose the most appropriate normalisation strategy for their particular study.

comparison of biological replicates. The Kholodenko group used mathematical models to simulate the effects of *+: , experimental normalisation and actual to " " data corroborate the+: results. % .

"

" use 2A “We clarified the quantitative of western data and@how the , * >blot " " normalisation strategy A " applied # to the " " data affects %the statistical testing, possibly increasing false positives or false . -+ + Dr "

negatives�, explained Andrea Degasperi from the Kholodenko group. % G % + / " " "

Western blotting provides experimental evidence that supports a given hypothesis

5 ;$

breast cancer, resistance is a common problem. G

/ + G 0 " '

E .

*G0' ., New research led by Conway Fellow, Prof + 1 inB William Gallagher the Irish B " Cancer " Cancer

Society Collaborative Research $ ("

&BD+ " " %

The Kholodenko group hope their study +: findings will not only act as a reference

to for scientists but also encourage them % . " include this critical information about data

articles. interpretation in published

" " " +: % ; Reference Degasperi et al. Evaluating Strategies to Normalise % A I" % B Biological Western Blot Data. PLoS ONE, Replicates

" of % 9(1): e87293. doi:10.1371/journal.pone.0087293, 2014.

"

Predicting response to endocrine therapies

G 55 8

= ! =

$ !

8 ! The majority of women diagnosed 5 with breast cancer have estrogen ! tumours, receptor (ER)-positive and 5 5 = are treated with tamoxifen. While this 5 $ how we treat drug has revolutionised

and is also used to validate data obtained from other techniques. Clarifying its quantitative use for decision making or statistical testing is necessary.

" " %

+ " &BD+ " $ Centre BREAST-PREDICT found ER (" % 0 that positive breast tumours with high levels " " of a protein called PRDX1

# G0' .had a better outcome than those with low PRDX1 levels. 4 " $ This study identified a unique role " the " (" for PRDX1 in protecting estrogen % . " " receptor from oxidative stress and so levels of " maintaining this protein in the targets % tumour cells. As tamoxifen the . G0' . 5 ;$ ;- + ' " " &BD+ $ % . $ " to treat " in agent used ovarian cancer with platinum

agents. combination It with works by interfering the spindle

;- + ' " " " " ;- > 1 B % B "

5 ;$ estrogen receptor, this research suggests ?!! % % ?=3=3! 5 ;$ that high levels of PRDX1 may maintain

! B % to this drug and improve responsiveness

patient survival.

5 ;$ ?

&BD+ 5 " " These findings may have implications for G F% / B% + B " breast cancer care in the future, as PRDX1 /% " " B 23 3 @ *C, could be used as a biomarker to guide 23 KP23C decisions regarding therapy. (publication pending in Breast Cancer Research)

Tailoring treatment in ovarian cancer

5 " " % /

"

% 4 for

The prognosis ovarian cancer

patients is

poor with only 3 out of 10 at least

women living 5 years after diagnosis. need Clinicians " " urgently the tools to provide a more accurate "

prognosis for patients in terms of whether particular chemotherapeutic agents will be of benefit in their treatment.

Q

microtubule dynamics to cause cell . cell a cycle arrest and death " (apoptosis), function mediated by MAD2.

“In this study, we were able to show that low MAD2 nuclear expression associates with a poorer response to chemotherapy and this was exemplified by a shorter time to recurrence of the disease in the patient cohort cancer subtype whose " included serous, endometrioid

" % and mixed histologies�, explained Barbara McGrogan, lead author and : the " doctoral candidate the " McCann in

group.

free survival irrespective of histological subtype could help guide clinicians as to whether chemotherapy will actually G0' . / + G benefit the patient.�. 5 ;$

Reference McGrogan B et al. Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer. Hum Pathol. 2014 Mar 27. pii: S0046-8177(14)00121-X. doi:10.1016/ j.humpath.2014.03.004. [Epub ahead of print] PMID: 24792619.

UCD researchers led by Conway Fellow, Dr Amanda McCann have now identified the a potential < protein MAD2 as 1 prognostic marker in a number of H F histological subtypes

of ovarian

8 cancer. This may help provide more tailored 5 5

approaches to the treatment of ovarian C cancer patients.

5 $

MAD22%A is one of the protein components G of spindle % assembly checkpoint " the

. (SAC) present in all eukaryotes that

prevents chromosomes from segregating incorrectly during cell division. Paclitaxel (Taxol) is the first-line chemotherapeutic " " %

"

- " "

" "

Serous endometrioid tumours are % 0 and biologically different, in clinical " however, practice they are" still treated similarly.

" " %

Dr McCann said, “The fact that decreased . expression identifies MAD2 nuclear " women 8 recurrence those with a shorter

" % 0 $

" " $ %

+ : 6' " " "

" "

" 7% . " " 1 " 0 & ' % Perinuclear MAD2 immunostaining in a moderately differentiated clear cell carcinoma (x40) ?

B "

% 9 8 + G 4 % )+ ' : % / E / *23 3,

Enabling oral drug delivery + ;$ to reach the blood. In collaboration the peptide reaching the blood from oral

From a patient perspective, tablets are preferable to injections when it comes to taking medication. The pharmaceutical company, Unigene : USA) 5

= ! (NJ, have designed a proprietary 5

7 > ? tablet formulation of calcitonin, an @ 5 anti-osteoporosis drug that

is usually 8 5 A injected. B/ B. B0,0$ 75

UCD researchers led by 8 5 Conway Fellow, 9 ! 9 5 Prof David Brayden have revealed the role played by one ingredient in this new 5 : 55 tablet, an additive called citric acid, in

5 enabling oral delivery of calcitonin. ( :- 7 > ? $

Normally, calcitonin is broken down in the gut as it is a small protein (peptide) and unable to permeate the gut wall

with Novo-Nordisk and Copenhagen University, the team showed that citric acid in the tablet acted only to . B and not " prevent breakdown to increase the epithelium of permeation across the

"

gut.

"

"

The means that there no " finding

was permeation enhancer in the calcitonin % 0 " + tablet and that the data achieved 1 B 1 85 in phase III F clinical trials by Unigene " arose

simply from preserving calcitonin intact " " " using agents approved in other products and presenting it to the gut wall in the % small intestine region. Prof David Brayden explained, “We worked out that the concentration of

administration was no more than 2%, which is still enough to compete with nasal competitor products for such a

" / / potent and exceptional agent. " G" / % :

+ G"

However, in future, less potent peptide products would enhancers to ' E - need $ get percentages of peptide to higher $ " the and this has toxicological blood F ) " implications.� " " % Reference Welling SH et al. The role of citric acid in oral peptide and protein formulations: Relationship between calcium chelation and proteolysis inhibition. Eur J Pharm Biopharm. 2014 Apr;86(3):544-51. doi: 10.1016/ j.ejpb.2013.12.017.

1

" " # " In Brief All living organisms require enzymes :

5 5 that are biological catalysts. These 8speed

catalysts up biological reactions so life is possible. Under biological :5 B0,0 C

! conditions, it would take about 5 : ( :-D 7,000 years for just half of peptide 9 9 $ bonds in a protein to be digested. Fortunately, such B proteolytic enzymes

as chymotrypsin allow us to digest " proteins than years. in hours rather " " % . " %from . the A recent publication group led

Prof $

by Conway Fellow, J.P.G Malthouse examines chymotrypsin how

can speed up reactions by " a factor of one thousand " million. The team found that one of the

%

mechanisms chymotrypsin uses is to

+ 1 + & " " J. K " L5C:MJ. K

In Pictures

increase the reactivity of its active site " " hydroxyl group by ~100,000 times.

" "

% Reproductive performance of cows affects the efficiency of milk and beef production . " J. K because of its influence on the calving to service " first interval, subsequent calving " and pattern, length of lactation culling

rates + rate, and culling for failure to conceive. % &

A % recent publication from Conway Fellow, Prof Mark Crowe updates earlier reviews on the topic of reproductive efficiency in " " dairy beef cows and factors J. K and

focuses " on contributing to resumption ovulation of " " and affecting uterine health in postpartum

% . dairy and beef cows. " " * , " "

" %

In seasonally calving herds, the aim is to achieve conception by 75 to 85 days, depending on breed, following parturition so that calving-to-calving intervals are maintained at 365 days. Reference Cleary JA, Doherty W, Evans P, Malthouse JP. Hemiacetal stabilization in a chymotrypsin inhibitor complex and the reactivity of the hydroxyl group of the catalytic serine residue of chymotrypsin. Biochim Biophys Acta. 2014 Jun;1844(6):1119-27. doi: 10.1016/ j.bbapap.2014.03.008. Epub 2014 Mar 21. M. A. Crowe, M. G. Diskin and E. J. Williams. Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows. Animal (2014) Mar 28: 1 -14

+ 23 3 ' ' *'' ,< B E B %

D " + E " " " + " " / 23 3% . " " " H + " Field testing eCDSS (electronic clinical descion support system) for connectivity in rural northern Malawi (l-r) Dr Chris Watson (UCD) and Dr John O’Donoghue (Imperial College London) as part of Managing Type 2 Diabetes in Malawi, Africa (MTIMA) project.

4

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" " $ B % 1 " B " / . 8 Dr Lorna Lopez (Cagney group) partners with her neuron teddy to give “Clues to understanding your brain� as part of Soapbox Science Dublin 2014

* % 8 I" % , 5 8 * % 8I" % , + * % I" % , "

" " %

Aine Lawlor launches ICORG’s first awareness campaign for International Clinical Trials Day with her assistants in the Institute.

! " # $% & $ '# ()*+* ,- .,/ /.0/ 1# ()*+* ,- .,/ /.0, 2# $ $ 3

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