UCD Conway Focus Summer 2015

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Issue 25,23 3 Summer 2015

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" Targeting inflammation obesity 1 !

New research led by Conway Fellow, % Professor Catherine Godson and

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Professor Kumar Sharma University in of California, San Diego shows that a (67 -! ! molecule found in the body can protect ! 8 ! against developing 5 obesity-related diseases by slowing, and possibly $ '

reversing, inflammation. findings !

The 7 could support a new therapeutic 1

9

approach to treating obesity and its 4

: (9 4 : associated conditions. % ! 5 6

$

Obesity is considered a risk factor for

diseases including diabetes, liver cirrhosis and chronic kidney disease. Adipose (fat ! " tissue) inflammation seems to be a # common denominator among these $

"

% obesity-related diseases. & " $ Inflammation is part of the body’s natural " %

response to injury. Lipoxins are molecules

' (" ) clear " that help to or resolve inflammation. study *+ This research set out to , investigate

and - the impact of a lipoxin, a synthetic . $ version " of the molecule, in a laboratory

" " % . model of "obesity.

" “This work aimed to mimic what occurs in %

health but becomes subverted in disease. Our findings show that reduced the /" lipoxins #

extent of liver and kidney disease caused " -+

+ % diet�, " BÜrgeson, by a high-fat said Dr Emma

+% "

" " first author and

" postdoctoral researcher with the Godson group who is currently working in the " University

of California % San Diego. . " " " “We found that a particular lipoxin various cells molecule (LipoxinA4) controls "

system of the immune with the overall

% . impact of reducing inflammation in adipose *01., as

the body tissue and, a result, protecting % ' effects " from the damaging of systemic

diseases that occur as a consequence of " obesity.� " " While the findings support the therapeutic " 01.%

potential of lipoxins, the team want to find a viable synthetic could - 23 alternative that

as "

" be developed a drug given that the is unstable molecule in its natural state expensive " The research " and to make. team $% 4 included synthetic chemists led by " Conway Guiry from " Fellow, Professor Patrick UCD " & School of Chemistry Chemical Biology. " "

% The research has shown that the synthetic

analogue of lipoxin [15(R)-Benzo-LXA4] 0 "

is also active, easier produce and

" " " to " consequently more cost effective. $

" This opens possibilities explore the use of to

similar molecules potential for

with the

greater efficiencies and effectiveness " "

while still being easy to produce and economic. "

$ "

“The findings of this research study % demonstrate the value and potential impact fundamental ' (" research. of Drawing on " expertise collaborative in synthetic "

biology chemistry, molecular and "

" have translational medicine, the team / 5 " with ' ' produced findings significant potential reduce inflammation, driver of to a critical "of the devastating consequences " " obesity-related diseases�, said Professor % Godson, Director of the UCD Catherine Diabetes Research Centre in & Complications 6.

UCD School of Medicine and (" UCD

"Conway Institute. " " ! "

“While this research study examined "

the action of lipoxin in a model of obesity, we 5 " %7 will now focus on its action in models of chronic kidney disease induced by obesity " " 8 and diabetes�.

+ % + & 9 : 0 : : . . 1 1 + + : . The research has ;%been through : : ' (" + funded ' % 23 3 / 22< a Marie Curie fellowship to Dr BĂśrgeson and ==*>,?@A >@

builds on previous research funded through Science Foundation Ireland and the Health Research Board. Reference BĂśrgeson et al. Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. Cell Metabolism, July 07, 2015 [ePub ahead of print] DOI: dx.doi.org/10.1016/j.cmet.2015.05.003

Director’s Message ) / Welcome!

In the last quarter, have been 1 there

8 8 significant for ; Conway Fellows

successes

including funding awards under the EU Horizon 2020 and Science Foundation " Ireland programmes. I am particularly " excited by the potential of a Marie $ Sklodowska-Curie Actions COFUND award â‚Ź2.1M. " (" worth " $

is % . TOPMed10 cross-institutional strategic " B and ' initiative that will leverage enhance interdisciplinary research strengths, ' =3 promote cooperation and cohesion, and A ;- 23 ;- " build translational research capacity " %

within personalised medicine across

the " Conway, Charles, Systems Biology 4 C

Ireland, UCD " Clinical Research Centre and the Schools. This

postdoctoral < fellowship programme support will

career development and interdisciplinary / training " in ‘omics’ driven personalised medicine " " " " for 10 high calibre experienced

researchers. This programme is primarily " meant "to stimulate % collaborations between basic and (pre)clinical researchers. It is open to

all UCD and I would 4 PIs, encourage you to avail of it. do not hesitate to contact Please

-+ me if interested. $ " I extend congratulations to " two new "

Conway Fellows; Dr Arun Kumar, UCD School of Veterinary Medicine " and Dr / Aurelie School of Medicine 0 Fabre,

UCD

23 3% & Medical Science and St Vincent’s University has interests 0 Hospital. " Arun in cardiovascular disease, diabetes, " " regenerative medicine, medical devices " and preclinical pharmacology. Aurelie has " + a key focus on lung fibrosis and initiated the immunohistochemistry associate " in technology the Institute designed to " provide specialised support to translational "

% research. Professor Kolch B Walter 4 : Director -+ + 0 "

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

+ 0 . 0

Prestigious award under EU Horizon 2020

5 5 5 ! 7 9

5

Fellow,

4 Brennan Conway Dr Lorraine ' : has been awarded an European : $ ' 7A ! Research Council (ERC) consolidator

5 ! grant worth â‚Ź2M over the next five years

! to develop new nutrition research tools. 1 ! 9 ' 7 1

Dr Brennan is based in UCD School 5 5 of B00"$ Agriculture & Food Science and

UCD Institute of Food & Health and

. 0 on . metabolism focuses and health using

B metabolomic techniques. % .

involves "

Metabolomics measuring small D; N B N sample molecules present in a biological " blood. such as glucose in urine or This " valuable " reveals information on metabolic are pathways in the body and "

how they

% altered in diet related diseases or different

" " " " exposure’ "

unreliable. %7 or ‘dietary are often

There is an increasing interest in +

.

identifying biomarkers to provide a more + " 6. . accurate measurement. As a technology, offers metabolomics great promise in this " " area.

% . For example, linking sugar-sweetened

to

" beverages health risks is controversial

and accurate without reliable dietary % .

assessment methods of food intake. " Dr 10 " Brennan recently published findings on "

a metabolomics approach to identify a panel of urinary biomarkers indicative of

%7

sugar-sweetened beverage intake from

B a. ) national food consumption survey.

in an This panel was "

" then validated acute " " intervention study. # "

dietary regimes.

identified 5 “We a panel of B

four biomarkers; G taurine, and formate, citrulline, isocitrate as markers of sugar-sweetened

beverage " intake. four metabolites in All

increased # % the urine directly after consuming sugar/ A 333 The 0 now sweetened beverages. challenge is to translate this panel of markers for use nutrition 0' % +" "

in epidemiology.

Traditional methods for collecting + B . information on a patient’s dietary habits

Brennan

Dr said, " “It is fantastic to get such funding as it . allows perform % researchers " to "

. B .

ERC Dr Brennan Through this award, "

in intends to apply metabolomics to *0' ,

nutrition research identify new biomarkers of dietary intake and .

" new dietary solutions that can tackle (" ! " " metabolic diseases such as diabetes. D; O B % 64 + " " % "

" 23 3 " "

" % 0 0' high risk research which could have major

" impacts in the " future. This will " "

support % . -+ " the expansion of my research + programme both 0'

in terms of people and equipment. " $ there were In total, over 2,500 applicants 24 European % from countries to this ERC

funding programme call, which is part

64 " " 0' of the EU’s Horizon 2020 budget. The " announced European Research Council $ % 372

awards totalling â‚Ź713M. to excellent " mid-career scientists. Reference

7 $ B A metabolomics approach to the identification of . % 6 " biomarkers of sugar-sweetened beverage intake. Gibbons B " et al. Am J Clin $ Nutr doi: 10.3945/ajcn.114.095604.(Epub Jan 21, 2015). 7% 0 " " 00 " B D; N " $ $ * / 5, " " %

00 " " (" " " "

" %

Heat map analysis showing the relation between 1H NMR spectral regions (ppm) and food group intakes (g/d).

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SFI Investigators Programme award success Conway Fellows, Professor Walter Kolch and Professor Grace Mulcahy have been awarded funding through the Science Foundation Ireland Investigators Programme to support research projects in malignant A melanoma and9 liver fluke infection 1 ! 7 over the next four years.

of resistance to these drugs and, based

responses and how this leads to chronic

avoid or overcome this resistance; and secondly to derive diagnostic biomarkers that predict drug combinations " "which will be most effective for individual patients�.

new effective vaccines to counteract the parasite and to protect farm animals from this disease�, Professor &0F said

Mulcahy.

on this understanding, to firstly design " disease, pathogenesis and death. Then, ' &0F personalised drug combinations that can using this new knowledge, we will develop

Professor Mulcahy also funded was through the SFI-DEL Investigators " " Programme that

supports Partnership % 6 " collaborative projects involving (" universities from Northern Ireland and the

#" "

Republic of Ireland.

B" "

" 7 % With QUB’s Professors John Dalton & Aaron Maule, Professor will look . " Mulcahy " at the application of new and emerging 1 " 0 - + technologies to develop vaccines against " % liver fluke. This has potential impact for the agricultural community across the island of Ireland.

5 %

Professor Grace Mulcahy, UCD School & " Medicine of Veterinary is funded to investigate the Application of New and Emerging Technologies Develop " " to

Vaccines Fasciola hepatica. against " % .

"

Liver infection (fasciolosis) is a global fluke " disease of farm animals and causes great $ losses to the agricultural " community. By merging recent technological advances % in molecular biotechnology, Professor Mulcahy hopes to reveal how liver fluke $ parasites interact hosts, D.GB with their animal cattle and sheep. (" %

Professor “The aim $ of this Kolch

" said, proposal is to investigate %the mechanisms

‘We will learn a molecular level how at " " these parasites hosts, how invade their "

they control and regulate immune " their

" " " "

. " " " "

Professor Walter Director of UCD @ > , Kolch,

Conway Institute and Systems Biology 5 5 Ireland aims to tackle the problem of 5 $ drug resistance in metastatic malignant melanoma personalising treatment. &0F by

Malignant melanoma is one the 0 % of deadliest cancers of its tendency + Cbecause

" to rapidly and its resistance spread 0 to drugs. The recent introduction of new 3 % drugs that inhibit Raf and MEK kinases has achieved remarkable successes,

" " treatment which unfortunately are of limited *D.GB, duration. 0 % .

% B

%

4 ("

$ %

" "

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

Distinguished Cournand lecture award is the first researcher from Ireland "

;- 1BK She honoured by the Society to deliver the

Conway clinician scientist, Dr Silke Ryan will deliver the prestigious Cournand lecture, to an expected audience of 20,000, at the forthcoming international congress of the European Respiratory $ ' Society (ERS). A A 9 A the â‚Ź"E+!+00 The ERS Congress, largest annual 5 7 respiratory meeting in the world, will take place in Amsterdam 26-29 September < from F 2015. ' (7 F 5 19. Dr Ryan is a Consultant in Respiratory and 5 $

Sleep Medicine at St. Vincent’s University Hospital and a Health Research Board- * % : % ", funded research fellow in the UCD School of " " "

Medicine and Medical Science at the UCD Conway Institute.

flagship lecture at its international congress in its 25-year history.

*+: , Dr Ryan was selected by the Society " over based " on the impact of+: her

research % " in a the last decade, which has. resulted " 2A better understanding of the mechanisms associated the development * >with " @ " of , various complications Acardiovascular

" # " in " obstructive %sleep apnoea (OSA). . -+ + " approach, Using a truly bench-to-bedside Dr Ryan’s research identified that % + has % G frequent oxygen preferentially / " fluctuations

" " activate inflammatory pathways known to

5 ;$

promote atherosclerosis, and these events are likely key mechanisms of cardiovascular disease processes in OSA. +: % . " " " " +: % ; % I" % B

" % Dr Silke Ryan

"

Revealing pathway to drug resistance in ovarian cancer

G 55 8

= ! UCD researchers led by Conway =

$ !UCD Fellow, Dr Amanda McCann,

8 & ! School of Medicine Medical Science 5 of have demonstrated the sequence ! molecular events leading to ovarian 5 5 = to the cancer cells becoming resistant effects of the5 $ chemotherapeutic drug,

paclitaxel.

G / + on G work 0 " This research builds previous '

E .

*G0' ., that pointed to microRNA miR-433 + 1 B B " " being associated with poor outcome for

women diagnosed with high grade serous $ ("

ovarian cancer. &BD+ " " The findings of % this All-Ireland

collaboration show that miR-433 can

5 cancer cells

to into cause ovarian move " " a state of permanent cell cycle arrest % As / (cellular senescence). if frozen in time,

these " cells are still viable but cannot

% 4 divide and grow.

targets actively

cells Paclitaxel dividing to cause cell " " death. When cells become senescent, they no longer divide "

so are

not susceptible to the effects of this drug.

" " %

“For first time, we demonstrated + the " &BD+that miR-433 induces "

cellular senescence $ and identified (" cyclin-dependent % 0 kinase 6 (CDK6) as a novel miR-433 associated " " gene�, said first author, Dr Karolina

# G0' . Weiner-Gorzel.

4 The team also demonstrated that the " $ to effect of cellular senescence can spread " " (" neighbouring cells causing them to also % resistant . " " This become to chemotherapy. " so-called ‘bystander senescence’ amplifies % the resistance to paclitaxel. . G0' .

;- + ' " "

" " ;- > 1 Reference Weiner-Gorzel al. Overexpression of the B %etB "

microRNA

miR-433 promotes resistance 5 ;$ to paclitaxel through the induction of cellular senescence in ovarian cancer cells. ?!! % % ?=3=3! 5 ;$ Cancer Medicine 2015 PMID: 25684390 doi: 10.1002/

! B % cam4.409 5 ;$ ? " " &BD+ 5 G F% / B% + B " /% " " B 23 3 @ *C, 23 KP23C

“The gateway to introducing new 5 ;$ ;- + ' therapies and improving outcomes for with ovarian women presenting cancer is " " &BD+how cells resistant understanding become $ to the effects of chemotherapy�, said % . $ Dr McCann. “This research shows that

has " miR-433 expression the potential a " of to become marker chemotherapy resistance in the clinical

setting.�

The Irish Health Research Board and the . " Mater Surgical Oncology Appeal funded this project.

Increased miR-433 expression influences the cellular morphology of A2780 cells G0' . / + G 5 ;$

Q Novel molecular ‘dimmer switch’ < 1 An international collaboration led by H Biomedical Dr ManelF Esteller, Bellvitge

Institute,

8 and Research Barcelona 5 5

involving UCD Conway researchers a control C has identified new

that partly 5 $ mechanism explains how

some melanomas have the ability to G the spread2%A around body, while others " % . do not.

findings, The study recently published in Nature Medicine have also revealed " that should " benefit from " those patients % particular targeted anti-cancer therapies. - " “This work set out to identify changes at "

" an epigenetic level – that is how genes particular " are regulated without DNA

" mutations - between tumour cells from

" that had % melanomas spread versus those that had not�, explained Conway : " Fellow, Professor William Gallagher of UCD "

School of Biomolecular & Biomedical Science and Chief Scientific Officer of % 0 OncoMark Ltd. "

" " We found a novel molecular ‘dimmer that " % protein switch’ unleashes a hidden signal and examined this epigenetic . switch hundreds of patient " in 8 tissues from across Europe. The signal emitted

makes skin cancers more aggressive " % 0 $

on the one hand but also makes them to treatment " susceptible with new " drugs�. $ %

+ : Professor Gallagher believes that these 6' findings

" research have potential for

" immediate clinical impact with respect " patients to pre-selecting melanoma that may preferentially respond to particular

approved " drugs. "

" 7% . " " this With more extensive research, novel 1 " 0 could ‘dimmer switch’ be & the direct target of' % new therapies in the longer-term. ? Reference Vizoso et al. Epigenetic activation of a cryptic TBC1D16 B M " transcript enhances melanoma progression by targeting

EGFR. Nat Med. 2015 Jun 1. doi: 10.1038/nm.3863. % 9 8 + [Epub ahead of print] G 4 % )+ ' : % / E / *23 3,

Ireland’s brightest scientific talents set for Lindau + ;$

Dr Mariana Bexiga, a postdoctoral researcher in the research group of Conway Fellow, Professor Jeremy : 5 = ! Simpson, has won a place at the 2015 5

7 > ? Lindau Nobel Laureate meeting taking place in Germany from 28 June -3 July. @ 5 8 5 A

Dr Bexiga another five of Ireland’s B/ B. joins B0,0$ 75 youngest and9 5 best science researchers 9 ! 8 5 who won places to participate in the prestigious week-long meeting involving 5 world’s : top scientists,

55

650 of the

5 including 66 former winners of Nobel prizes. ( :- 7 > ? $ The six secured their places in a highly-

competitive international competition and will be funded to participate by the Irish Research Council. . B

"

Nobel The annual Lindau Laureate

"

meetings provide a globally recognised forum the transfer of

knowledge for

" " between " generations of scientists;

the scientific elite of today and the % 0 " brightest + minds of B the future internationally. 1 1 85 " F

“Being invited to " take part in " this event " is

a huge honour for any researcher, but the fact that six Irish young people are % participating with the best in the world is just fabulous,� said Dr Eucharia Meehan, director of the Irish Research Council.

" / / " G" / % : + G" ' E - $ $ " F ) " " " % (L-R) Roman Stilling, Owen Byrne, Jessica Hayes, Shalini Singh, Thomas Higgins and Mariana Bexiga.

1 " " # "

Election to the Royal Irish Academy : 5 5

Conway Fellow, Professor Geraldine 8

Butler of UCD Biomolecular School of and is one of four :5 Biomedical B0,0 Science

C

! UCD professors newly : elected to the 5 ( :-D ranks of the Royal Irish Academy in 9 9 $ recognition of outstanding academic B is

achievements. This the highest academic honour in " Ireland and membership is reserved for " " those who

% . " have achieved distinction in education % . and research. $

Professor Butler is an expert on the " " and genomics, evolution virulence

% yeasts. She led an of pathogenic international that sequenced + 1 consortium + & " " J. K " L5C:MJ. K

" "

the genomes of eight and " " Candida species, that research was published in Nature in % 2009. She has pioneered high throughput gene knockoutJ. K technology for Candida . " parapsilosis, a pathogen newborn " affecting infants. " +

Professor Butler is also the programme %for & director the first Irish based PhD

programme funded by the Wellcome Trust. % The PhD programme in Computational Infection Biology trains scientists to computational methods " " with integrate J. K

" biological research focused on infectious " " diseases.

% . " " * , " "

" %

(L-R): Professor Ian O’Donnell, UCD; Professor Orla Feely, UCD Vice-President for Research, Innovation and Impact; UCD President, Professor Andrew J Deeks; Professor Mary E. Daly, President of the Royal Irish Academy; Professor Geraldine Butler, UCD and Professor Nicholas Daly, UCD. + 23 3 ' ' *'' ,< B E B %

Accessible science: 2015 Engage Seminars

D " + E " "

Conway PhD student, Paul Lavin (McGee group) won the 2015 Engage Seminars science communication "a presentation + " competition with late-stage " entitled, Flip off Cancer. Six / 23 3% .

doctoral PhD students presented their and " way " research in a clear accessible " of

to an audience friends, family and by colleagues. Organised UCD School H + Biomedical " of Biomolecular and Science, the annual competition was hosted this year by Dr Aoibinn Ni Shuilleabhain and took place in the UCD O’Brien Centre for Science on 09 April.

4

1

Paul spoke about his research on Cyclophilin A, a protein that can turn off cancer cell growth. Many cancer cause collateral " damage therapies in the as " destroy $ body they try to cancer cells. Paul hopes that revealing proteins those being switched on/off by Cyclophilin A B could allow design drug manufacturers to targeted %therapies 1 " to Flip off Cancer B without collateral " / . damage. 8

(Hensey group), Catherine Tighe (Guiry group) and Ines Freitas (Wellcome Trust Computational Infection Biology PhD * % 8 I" % , programme) also did justice to their brief of to5 8 their research using plain English make accessible. * % 8I" % , + * % I" % , "

" " %

Jennifer Cleary (Malthouse gp) was placed second for her seminar that demystified nuclear magnetic resonance to basically just magnets and radio waves. Hayley Beaton (Crean group), Cormac McGarry

Institute Manager (Communications & Education) " Belfield, ! Dublin 4,

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

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