UCD Conway Focus Spring 2015

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Issue 24,23 3 Spring 2015

4 " Lowering diabetes risk in obesity 1 !

% high saturated-fat Eating food is

5 and, contributing to the rise in 6

obesity as a consequence, this increases the risk (67 -! !

of insulin resistance and type 2 diabetes. New ! 8 ! research published in the scientific 5 that journal Diabetes shows replacing $ '

saturated fatty acids with monounsatu ! 7 diet rated fatty acids

within a high-fat 1

9 can reduce inflammation in fat tissue and 4

: (9 4 :- increase insulin sensitivity.

% ! 5 6

$

UCD researchers led by Conway Fellow,

Professor Helen Roche, Associate

Professor of Nutrigenomics UCD School of Public

in ! " Health, Physiotherapy & Population Science and UCD Institute of Food # & Health, $

" types compared how different of % fats & " controlled the release of IL-1β, a powerful $ immune system protein. " % This protein the development of ' (" ) triggers "

insulin resistance and type 2 diabetes. *+ , Obese individuals have levels of IL-1β higher - circulating in their system, which is thought .

" $

" " " from % . tissue. to originate adipose or fatty

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

" " Before IL-1β is released, primed

" cells are to

team have produce pro-IL-1β. The research " shown that replacing saturated fats with

% monounsaturated fats in a high fat diet

reduced pro-IL-1β priming in adipose . the " " " tissue. This had a knock-on reduc effect of ing the extent inflammation adipose "

of in tissue. and increasing insulin sensitivity.

% *01., “We have demonstrated for " the first time % ' that dietary monounsaturated fatty acids " can lower IL-1β mediated insulin resistance and " adipose dysfunction despite obesityâ€?, " said Dr Orla Finucane, postdoctoral " group 01.% and first researcher in the Roche author of the article. - 23 " " This study involved mice a high-fat feeding diet either with saturated fatty enriched " " acids or monounsaturated The $% 4 fatty acids.

" team used metabolic and genetic " analysis

to determine the extent of inflammation " and insulin To translate their tolerance. " "

findings from animal to humans, they then

% reanalysed data from human studies with

0 " detailed dietary fat data to discriminate

" " " " between fat quantity and composition. $ "

" " "

Director’s Message ) /

Welcome!

senior Recently, a number of Conway

8 8 and early1 career researchers have been recognised contributions

for outstanding ; and excellence in research. Most notably, Professor Cormac received the 2014 " Taylor Nature mid-career award " for mentoring in science Professor Des Higgins was $ while appointed a Fellow of the International " (" Society for Computational Biology. A " $ research paper by Des Higgins that set the

% . " B ' ' =3 ;- 23 ;- " A " %

international standard for DNA sequence analysis featured in Nature’s Top 10 most 4 " C

of all highly cited research publications " time.

$ "

Professor Helen Roche says, % “The findings of this study are exciting as we have shown ' (" at a molecular level how monounsaturated " fatty acids interact with immune cells within " " adipose tissue to reduce the risk of type 2 " diabetes developing. / 5 " ' '

The molecular pathways involved

" include a " metabolic " sensor called AMP-activated protein % kinase (AMPK) that also regulates inflammation. Type 2 diabetes is routinely & with 6. treated a drug that targets AMPK called However, ("

" Metformin. there have been recent " " ! " adverse concerns suggesting potential associated with cardiovascular side effects " this drug. On the basis of this research, 5 " %7 we propose that targeting AMPK through means would be both cost effective dietary " to and beneficial the " patientâ€?. 8 + % + & 9 : 0 : : . . 1 1 + + : . Reference : : ' (" fatty ;% acid + enriched ' % 23 3 22< Monounsaturated high/ fat-diets ==*>,?@A >@ impede adipose NLRP3 inflammasome mediated IL-1β

secretion and insulin resistance despite obesity. Finucane et al. Diabetes (e-pub ahead of print) January 27, 2015, doi:10.2337/db14-1098

Development Award (TIDA) programme. Researchers also won in four categories of " Awards. / the 2014 Irish Laboratory 0

23 3%

< Irish Cardiac Dr Chris Watson won the / " Society Brian Maurer Young Investigator " " Dr " was joint " award while Orla Galvin

Started

winner of the Get Technology

of " Venture Programme run "

as part % the Science Foundation Ireland /

I congratulate these individuals while acknowledging those who have been 0 " all successful in recent competitive funding " " awards and publications. of these " All achievements to the talent are

testament " + and calibre of scientists that are the cornerstone of this Institute.

4 -+ $ " " "

B 4 : -+ + 0 "

Enterprise Ireland Technology Innovation

" Walter " Kolch Professor "

% Director

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

+ 0 . 0

CURAM to meet R&D needs of medical device sector 5 5

Conway David

5 5 ! Fellow, 7 Professor 9 Brayden, School of Veterinary UCD

4 Medicine is one four: co-principal of ' investigators leading the newly : $ ' 7A ! awarded Science Foundation Ireland

5 ! Centre in Medical Devices (CURAM).

! 1 ! 9 ' CURAM will receive â‚Ź28M over the next 7 1

six years (2015-2021) to address the R&D 5 5 needs of the Irish medical device sector. B00"$ The national Centre is a public-private

partnership involving financial input from . 0 . the State as well as financial andB in-kind commitments up to 30 medical from % device including Boston .

companies "

Scientific, Medtronic and Covidien. D; N B N " The "

medical device industry employs " up to 25,000 people in Ireland and is a " significant contributor to the export-led

% national economic recovery.

. B . “Essentially,

CURAM research encompasses questions about "

how biomaterials can be used as scaffolds *0' ,

and delivery systems for stem cells and therapeutics in medical implants designed . " for regenerating many tissues including (" ! " " heart, spinal cord, and cartilage�, said Prof D; O Brayden. B % + B . “The 64 core programme will design + " new functionalised for devices materials " that can eventually move industry-funded % into "

" 23 3 " "

" " "

‘spoke’ projects once successfully

through " proof-of-principle preclinical "

studies. %7 + the

we are .

In interim, establishing ‘spoke’ + " 6. on

. projects to work R&D questions for some existing and drug

devices molecules device " solutions. requiring " In the initial period,. we plan to funding % carry clinical out several device trials led by clinicians in Irish hospitals show

to " evidence of translation�.

% . "

With a background drug delivery, Prof 10 " in Brayden will focus particularly on drug " device combinations including new device %7 constructs for buccal and intestinal drug delivery. . ) B

"

"

“One of the attractions of the is " " Centre the opportunities collaborate with to

# " experts in other disciplines including 5 B

engineering, physics and electronics as G well as accessing a fantastic range of

" national expertise.� # %

CURAM provide education / will A 333 0 and training opportunities for over 50

PhD candidates and +" 25 postdoctoral 0' % "

researchers to become future research

leaders in the university and

medical " device sectors. A proposed outreach % . " " programme and significant business 00 " development efforts will " (" create a pipeline projects and clients " " of for "

years to come.

" %

Prof co-PIs in CURAM are Prof Brayden’s

"

% 0 Abhay Pandit, Prof 0' CURAM Director; Tim O’Brien and from NUI,

Prof

" Lokesh " Joshi " "

Galway. UCD scientists also participating % . -+ + " in the Centre core programme include 0' Conway Fellow, Prof Jeremy Simpson, " UCD School of $ Biology & Environmental

Science; Dr Wenxin Wang, UCD School % Sciences, UCD of Medicine & Medical

Charles Institute; Dr Madeleine 64 " Lowery, " 0' UCD School of Electrical, Electronic & " Communications Engineering. $ % . "

7 $ B . % 6 " $ B " 7% 0 " " 00 " B D; N " $ $ * / 5, " " %

Prof David Brayden (first left) pictured beside Prof Abhay Pandit, CURAM Director at the SFI Research Centre Awards announcement made by Minister for Jobs, Enterprise & Innovation, Richard Bruton T.D. and Minister of State, Damien English T.D.

FutureHealth: accelerating health science innovations UCD in partnership with the NDRC shortlisted 10 start-up ideas to participate in FutureHealth, a new pre-accelerator programme created to focus exclusively on the support of early stage ‘healthtech’ ventures.

-

to use, but often rely on disjointed information from individual clinical trials or reports summarising entire patient groups.

Dr Baljuls is taking part in the programme as a skilled participant on Dr Charles Nwankire’s team, ‘SensoMapp’. Other team members include Cristina Esteve, Valorisation & Technology Transfer Officer, FundaciĂł (Technology); Gerry &0F Chief Advisor

Rafferty, Health (Clinician); Gaynor, % B Caroline Commercial Lead, NUI Ltd Galway & Director, Situla Consultants (Business); Barrett (Creative). Shelly " "

' &0F "

A 1 ! 9 the 7 The FutureHealth team, with support of most successful of a selection Ireland’s 5 % healthcare entrepreneurs and investors, @ > , clinicians, and

will enable researchers 5 5 entrepreneurs to come together, form teams and build a commercial proposition 5 $

and a convincing investment case.

&0F

Dirk Fey, " postdoctoral Dr a senior 0 % researcher in Systems Biology Ireland (SBI) + Con the

" claimed his place FutureHealth following a 0 pitch programme three minute % of his 3proposal, ‘OncoNamics’. " " As one of the ten successful idea owners, is Dirk now heading a*D.GB, team of six skilled 0 % including . participants, SBI’s Maciej to

business Dobrzynski, test the potential " $ of ‘OncoNamics’ over the next couple of % weeks. "

“Oncologists have to decide, in each " individual case, how to treat their patients "

" or drug-combinations and what drug

I have developed an algorithm for " " simulating the signalling behaviour in

of tumour cells individual patients. it possible %to predict the This makes best possible treatment option for each & " individual patient and has the potential to radically transform care planning.� " "

" % . Speaking at the launch of the pre B" NDRC " accelerator, Ben Hurley CEO “With FutureHealth " we to said: want empower health $ sector startups with a " world.� digital heart to change the %

During the programme, the teams will $ get unrivalled access to leading mentors D.GB from the health sciences, seasoned ("

% technology entrepreneurs and the 4 (" as investment community as well a process " " proven to test their ideas. "

opportunity " to “It’s a great acquire skills $ % new and to extend my network in Ireland. I am really delighted to join this . " " programme�, said Dr Angela Baljuls, a researcher " " senior postdoctoral also from SBI.

% 6 " ("

#" "

" " " 7 %

. " " 1 " 0 - + " %

? / &0F % B" / (" +% % " F 23 3 >CC >A

Futurehealth ‘OncoNamics’ team (L-R): Stephen O’Brien, Helen Rea, Nuala Hannon, Paddy Dennis, Dirk Fey, Maciej Dobrzynski, Colm Lynam.

Role of anti-fibrotic receptors in regulating pulmonary fibrosis In Ireland, 120 people die each year as a result of idiopathic pulmonary fibrosis (IPF). There are limited treatment options for this chronic progressive lung disease typified by the remodelling of lung tissue and blood vessels.

"

;- 1BK $ '

A A A Researchers led9 by Conway Fellow, Professor Michael Keane, UCD School â‚Ź"E+!+00 of Medicine & Medical and St 5

Science 7 Vincent’s University honing < Hospital are F in on cells involved in triggering ' and (7 F controlling in 5 an attempt to find fibrosis

19. new therapeutic avenues. 5 $

IL-13 a profibrotic cytokine involved in is* % : % ", lung fibrosis. The effects of

this protein " " "

are regulated by a complex receptor system including the IL-13RÎą2 molecule. Until

recently, the IL-13RÎą2 molecule was seen as a non-signalling decoy receptor working to limit the bioavailability of IL-13 and its profibrotic effect. Recent studies suggest that IL-13RÎą2 may play a role in signalling. *+: ,of A subfamily chemokines (CXC) are " " leukocyte +: trafficking involved in promoting % . " and in recruiting mesenchymal progenitor The

" 2A the cells like fibrocytes. team studied role of CXCR3 in the regulation of , IL 13RÎą2 * > " @ " expression. A " # " " %

They compared the regulation of IL. -+ 13RÎą2 by+ IL-13 in cells "

with and without the CXCR3 receptor and concluded that % + % G CXCR3 is required for " " the IL-13 / " mediated upregulation of IL-13RÎą2 in pulmonary fibroblasts.

5 ;$

“We have found that the expression of one of the IL-13 receptors, IL-13RÎą2, is dependent on the expression of another anti-fibrotic receptor, CXCR3â€?, says Dr Rosemary Kane, senior scientist in the Keane group.

+: “Having a better understanding the function of CXCR3 in IL-13 mediated lung . " injury may lead to % novel approaches to combat the development of pulmonary " " " fibrosisâ€?. Reference CXCR3 is required for the IL-13 mediated +: % ; upregulation of IL-13RÎą2 pulmonary fibroblasts. Barnes et al.B Am J %

in I" % Respir Cell Mol Biol. 2014 Dec 16. [Epub ahead of print]

" %

"

Arming nanoparticles for cancer diagnosis and treatment G 55 8

UCD researchers led by Conway

= ! Fellows, Professor Gil Lee, UCD School =

$ ! of Chemistry & Chemical Biology

8 Walter ! and Professor Kolch, Systems 5 Biology Ireland have successfully ! manipulated nanoparticles to target 5 5 = two human breast cancer cell lines 5 $ as a tool in cancer diagnosis and treatment.

G / + G 0 " Coating nanoparticles with different '

E . *G0' ., substances allows their interaction with 1 B B " " cells to+ be specifically tuned. The team

synthesised nanorods with a long iron ("

segment coated with $ polyethylene glycol &BD+

and

a short gold tip coated with single % layer " " of the protein, heregulin (HRG). 5 HRG binds to and activates the ErbB " " receptors family of protein that are % / cancers overexpressed in certain breast

" As and linked with poor prognosis.

% 4 leads

ErbB2 overexpression to enhanced

sensitivity

to certain drugs, the team " " "

" " %

believe that using Fe-Au functionalised nanorods with these drugs could&BD+ be + " beneficial cancer treatment. " in $

(" % 0

They first characterised and tuned " " the nanorod-cell

# interaction G0' . before assessing response to mechanical cellular stimulation using a novel microfluidic 4

device with an optical microscope, " $ integrated electromagnetic tweezers and " " (" a microfluidic chip. % . " " " The team monitored the interaction of nanorods individual with two %human

! B %

“The results are a positive indication 5 ;$ ? for nanoscale targeting and localised " " &BD+ 5 manipulation of cancer cells with a G F% / B% + B " specific receptor profile.� /% " " B 23 3 @ *C, 23 KP23C

breast cancer the . G0' . cell lines expressing ErbB family of receptors. When the HRG5 ;$ ;- + ' nanorods to cancer expressing bind cells ErbB, they kick off a cascade of signalling " " &BD+ events that lead to cell death. $ % . $ “Using magnetic tweezers to stretch cells, we were able to " further activate pathways " cell signalling to trigger cell

death. This was even more effective in . "

Not beyond us: World Cancer Day 2015 Q

;- + ' " "

causing cancer cell death than magnetic " " ;- > 1 hyperthermia, the other therapeutic B % B "

approach we assessed�, explained 5 ;$ first author and Dr Devrim Klinic, ?!! % % ?=3=3! 5 ;$ postdoctoral fellow in the Lee group.

ErbB2 receptor clustering following HRG–nanorod binding to MCF7 cells. G0' . / + G 5 ;$

in particular, where genetic mutations in “Bringing together like-minded

cancer scramble messages in biological researchers from different academic

Cancer researchers from across the Institute gathered to mark World Cancer Day 2015 on February 4th. This year the campaign emphasised a < proactive approach to the1 fight against H cancer byF highlighting solutions that exist the continuum of cancer

across

8 care, and those that 5 are within our

5 reach. C

5 $

“We are meeting the challenge cancer G 2%Aus at presents with by tackling cancer its " roots

. very and % by personalising therapies

to each individual patient�, says Professor Walter Kolch, Director, UCD Conway Institute and Systems Biology Ireland. " " " %

“We focus on the communication - that control " and coordinate

networks "

" the behaviour of cells in our bodies and, "

signalling networks.�

strategy " This of personalised medicine by % is " also one shared Conway Fellow, Professor William Gallagher, Director, : " BREAST-PREDICT. "

‘We are meeting the challenge cancer % 0 harnessing

presents us with by all of the available " on information breast cancer

" patients and their" tumours to predict patients

" % how best to treat based on the

individual characteristics of their cancer.

. " 8 The role of collaborative networks in is

meeting the challenge highlighted " %Watson, 0 $

by Professor William Conway and President " Irish Fellow of the " $ for Association Cancer Research. %

institutions and hospitals across Ireland in a co-ordinated way provides us with an +

: excellent environment to tackle important 6'

questions in relation to " prostate cancer diagnosis, prognosis new therapies�. and " "

" "

" 7% . " " 1 " 0 & ' % ? B "

% 9 8 + Institute cancer marking World Cancer G researchers 4 % )+ ' Day 2015 / E / *23 3, : %

Supplemented Mediterranean diet for healthy ageing different diets for four week periods; a After eating the Western diet rich + ;$ Mediterranean diet with coenzyme Q ; in saturated fat, we found greater

Eating a Mediterranean diet supplemented with coenzyme Q10 may benefit healthy ageing according to new research from UCD researchers : by 5

= ! led Conway Fellow, Dr Lorraine 5 with 7 > ? Brennan in collaboration international colleagues. @ 5

8 5 A Antioxidants protect against the damage B/ B. B0,0$ 75 caused unstable molecules or ‘free 9 !by 9 5 8 5 radicals’ in cells. One of the hallmarks of ageing is the chronic oxidative stress 5 when : 55 arising the balance tips away

from antioxidants. 5 protective The resulting damage can lead cardiovascular and ( : 7 to > ? $

neurodegenerative diseases.

This study compared urinary metabolic profiles of elderly people on diets with varying saturated fat levels. Ten individuals followed each of four

10 a Mediterranean diet alone; a Western diet rich in saturated fat; a low-fat, high carbohydrate diet enriched . B " in n-3 polyunsaturated fat.

"

The Mediterranean on "

" diet focuses

antioxidant-rich and " fruit, vegetables grains with saturated fats. When % 0 few " + supplemented with coenzyme q10 (CoQ), 1 B 1 85 a " potent F lipid soluble antioxidant, this diet may combat the processes related to " " " chronic oxidative stress.

% “We found that there were greater hippurate levels in the urine after consuming the Mediterranean diet with coenzyme Q10. Although not directly beneficial by itself, hippurate is indicative of gut microflora activity�, said Dr Brennan.

phenylacetylglycine excretion. Also generated from gut microbiota metabolism, is often phenylacetylglycine " / / overexpressed disease with " inG"

/ %levels : being significantly higher in failure + heart G"

patients for example�. ' E - $ $

"

Interestingly, the team saw greater F ) " benefits of the supplemented " Mediterranean diet in women. As the participants female are postmenopausal without any of " % the additional antioxidant benefits attributable to estrogen levels, the difference may be related to diversity of gut microflora in men and women. Reference Effects of the Mediterranean Diet Supplemented With Coenzyme Q10 on Metabolomic Profiles in Elderly Men and Women. Gonzalez-Guardia et al. J Gerontol A Biol Sci Med Sci. 2015 January;70 (1):78–84 doi:10.1093/gerona/ glu098

1 " " # "

Engaging the next generation of scientists : 5 5 8 Over 550 children UCD C

! :5 B0,0

joined researchers learn about to 5 : pipetting ( :-D and material properties through fun 9 9 $

experiments at the 2015 BT Young B & Exhibition

Scientist Technology in RDS, the Dublin. The " team of PhD and were " " postdoctoral scientists on hand . " to give the % children an interactive % . experience of basic laboratory skills.

$ The children got the opportunity to " " experiment with petri dishes, pipettes,

% gels and coloured liquids as they learnt

the difference a hydrophobic + 1 between + & and Dr Robert hydrophilic

" effect. " Schwamborn and Dr Susan Kennedy J. K " L5C:MJ. K (Systems Biology Ireland), Kate Connor

" " " " %

and Jennifer Cleary (UCD Conway Institute) . Jonathan " O’Keefe-Ahern J. K and (UCD Charles " Institute of Dermatology) enjoyed the opportunity work passionate " to with these budding scientists.

+ % &

The activities were run as part of a pilot

programme for the Amgen Biotech % Experience, a science education initiative that provides professional development " " training for secondary school teachers, J. K " learning materials, and research-grade " classroom " equipment and supplies for the

The programme % . laboratory. is being coordinated by Systems Biology Ireland " " * and the Biomedical Diagnostics Institute, , "

Dublin City University. "

" %

PhD student, Kate Connor pictured at 2015 BT Young Scientist Technology Exhibition with young workshop + & 23 3 ' ' *'' ,< B E B % participants

Recognising laboratory excellence

D " + E " "

UCD researchers and staff swooped four trophies at the 2014 Irish Laboratory Awards at a gala evening " +

" hosted by comedian, Neil Delamere December 3rd. " on The competition / 23 3%and . celebrates the

very recognises organisations, " " best laboratories, and " people in the industry. HFellow, + Professor " Conway William

Gallagher accepted the award for Laboratory Team of the Year on behalf of the Cancer Biology & Therapeutics Laboratory, UCD Conway Institute that he jointly leads with Conway Fellow, Dr Darran O’Connor.

4

1

The Collaboration Achievement Award went to BREAST-PREDICT, the Irish Cancer Society Collaborative Cancer Research that " Centre aims to personalise breast " Centre $ cancer treatment. manager, Dr Fiona Lanigan the trophy on accepted behalf of the B team.

Amaya Garcia % 1 "from

Systems Biology B Ireland the category of Laboratory " won / . 8 Staff Member of the Year and OncoMark won the Medical Laboratory of the Year category. Based in NovaUCD, Oncomark focuses on new diagnostics and therapeutic targets to improve the quality of life for cancer patients. Dr MĂĄirĂ­n Rafferty, CEO accepted the award on behalf of the team that includes Professor William Gallagher.

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

" " %

Professor William Gallagher receives the award for Laboratory Team of the Year for the Cancer Biology & Therapeutics Laboratory, UCD Conway Institute from Dermot Harrington, Managing Director, Antech Solutions.

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

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