UCD Conway Focus Autumn 2015

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Issue 26,23 3 Autumn 2015

4 winners of

Gold " Joint 2015 UCD Conway Medal 1 !

Dr Melinda Halasz and Dr Alison Rey % nolds are joint winners of the 2015 UCD

5 6

Conway respective gold medal for their research projects to find new treatment (67 -! !

in a highly aggressive child approaches ! 8 ! hood cancer and in a condition that can 5 lead to blindness. $ '

!

7 Neuroblastomas arise in children when 1

9

a cancer causing gene (oncogene) called 4

: (9 4 :-

MYCN is amplified. Currently, there % ! 5 are no drugs available that can successfully block 6

$

this oncogene. Dr Melinda Halasz (Prof Wal-

ter Kolch group) hopes to find a therapeutic approach to treating this cancer by identify ! " ing and targeting key proteins that interact # with the MYCN oncogene. This $

" approach

% seems promising as Melinda has been able & " to reduce the size of a

tumour in a zebrafish $ model of " % neuroblastoma by targeting a key

protein in gene regulation (RNA splicing

' (" ) inhibitor). " *+ ,

Breandan - Kennedy Dr Alison Reynolds (Dr . $ group) " is trying to identify a drug to treat

" " " % . retinal neovascularisation. This feature of

as " diseases such diabetic retinopathy can lead to blindness. Alison brought a candi %

date compound identified from 1800 com-

pounds forward further experiments /" into # based its ability to stop new blood vessel " on -+ + % eye of

" growth in the a newborn zebrafish. +% "

" " The compound works by blocking a protein

" involved in inflammation and angiogen esis called CYSLT1. It was " well tolerated in zebrafish, mice, and human cell lines. %

Synthetic versions of the original lead

. " " " compound were made, tested for efficacy has for one and a patent now been granted "

drugs. of these novel

% . *01., and

their Drs Halasz Reynolds accepted % Vice award from' Professor Orla " Feely, UCD

President for Research, Innovation and " Impact. Speaking at the ceremony to close " the 2015 UCD Conway Festival of Research " & Innovation on Thursday, 10 September, " 01.%

Professor Feely said, “I applaud these two

early clearly - career 23researchers who have the judges "

" impressed not only with the and its potential quality of their research "

" translational applications but also their $% 4

" ability to articulate this work concisely.� " " against Drs Halasz and Reynolds competed poster category " "

three other winners for

% the overall prize. These included Dr Sinead

Walsh (Prof Keane group) for 0 Michael "

‘Investigating the origins of the myofibroblast

" " " " in pulmonary fibrosis’; Rebecca (Dr $

Reilly " Judith Coppinger group) ‘Inhibition of the for

PI3K/AKT/mTOR improves traffick pathway

ing of Δ508-CFTR in Cystic Fibrosis’; Agata " "

Blasiak (Prof Gil Lee group) for ‘Differential "

$ "

growth behaviour in CNS neurons in response % to local axonal vs. global Netrin-1 treatment is ' (" mediated by Ca2+ , cAMP signalling and DCC " dynamics’. " "

The judging panel comprised " / 5 " ' ' Professors Anne Ferguson-Smith, University Cambridge, of UK; Colin Hill, University " College Cork and Christoph Lengauer, CSO " of Blueprint " Medicines, Cambridge, USA % who were plenary speakers at the event. The 2015 Conway gold medal sponsor & 6. Festival

is Cruinn Diagnostics. (" " " " ! " " 5 " %7

" " 8 + % + & 9 : 0 : : . . 1 1 + + : . : : ' (" ;% + ' % 23 3 / 22< ==*>,?@A >@

(L-R): 2015 UCD Conway Festival prizewinners: Rebecca Reilly, Dr Sinead Walsh, Dr Melinda Halasz, Dr Alison Reynolds, Agata Blasiak.

Director’s Message ) / Welcome!

training opportunities to best advantage.

In the last quarter, 1 we

8celebrated the 8 research achievements of Conway

;

4 " C During October, we opened doors " our to women who have

had a breast cancer < diagnosis. Researchers staff from and

across UCD Conway, Systems / Biology " Ireland " and BREAST-PREDICT worked with " " " patient advocacy Donna

group,

Europa

Ireland to deliver a programme of " talks and

" laboratory % tours in this open house event.

scientists over the previous twelve months in the 2015 UCD Conway Festival of " Research & Innovation. "

$ Along with plenary speakers, Anne " (" Ferguson-Smith (Cambridge), Colin Hill "

(University College Cork) and $ Christoph

Medicines %Inc), . I Lengauer (Blueprint was " senior ' delightedB to welcome managers from ICON plc, Novartis, Pfizer and S3=3 ' Group an ;early career researcher ; to 23 " forum A on how to tailor career development " %

The feedback from participants was 4 inspiring and

reinforces belief that the -+ opening the pathway scientist $ between and patient vital as we move together " is towards personalised medicine. As one " "

participant said; “I hope that by putting faces their cancer cells, and on " scientists /

researchers been encouraged 0 have

to 23 3% continue their vital work�. 0 "

Professor Walter Kolch " " Director

" " + " " "

% B 4 : -+ + 0 "

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

+ 0 . 0

Success in drug delivery industry- academic collaborations

5 5 5 ! 7 9

5 between

4 The collaboration Irish drug ' : delivery company, Sigmoid Pharma : $ ' 7A ! and two research teams led by Conway

5 Fellows, Professors Cormac ! Taylor and David Brayden to strengthen

! continues with new publications a recent 1 ! 9 and ' Irish Research Council EMBARK PhD 7 1

scholarship award to Douglas Halligan. 5 5 B00"$

When the Taylor group showed that

. 0 . hydroxylase inhibitors represent a new B therapeutic approach to

inflammatory bowel disease, they teamed up with % .

"

Sigmoid Pharma to formulate drugs in D; N delivery B N a way that allows specific of a " of low dose to the diseased region the " " gastrointestinal tract in order to minimise unwanted side effects. "

%

Their recent co-authored publication . Journal B . in the of Controlled Release

have been demonstrates that the team "

target the gut able to specifically with

hydroxylase inhibitors for *0' , therapeutic benefit while minimising side effects.

. " (" ! " "

Inflammatory bowel disease is a prevalent and serious condition that affects large D; O

B a %

number of people in Ireland today with

" " " " Halligan "

his %7 Douglas will conduct doctoral

research between Taylor group in UCD +

the .

Conway Institute and Sigmoid Pharma in + " 6. . The Invent Centre, DCU.

" " The Brayden group has been working with on % . oral Sigmoid Pharma improving drug systems across They delivery the intestine.

recently studied the

effects of " different

formulation components on intestinal % . stages " peptide permeability at different of 10 " synthesis.

" % 0 0' the two systems. We also proved that the

process

" was " formulation mild " "

and did not % . the as -+ " denature calcitonin, this+ is critical for 0' system�. any oral peptide " $ This research may pave the way to the % further for develop formulation

small intestinal delivery of a variety of

"

64 " " 0' peptides such as insulin that are currently administered "

being by injections. Oral $ % . improve drug

delivery would potentially " patient compliance in taking medication and also present the active agents in a

7way $ more physiological to theB body than . % 6 " which down

injections, are broken in the and $ are B across " intestine not

permeable the intestinal barrier. 7%

"

0 " " 00 " B Reference

hydroxylase " Murtaza M et al.D; N Targeted delivery of the inhibitor DMOG provides enhanced efficacy with reduced $ systemic exposure in a murine model of colitis. Journal $ * / 5,

" of Controlled Release 2015 November doi:10.1016/ j.jconrel.2015.09.022 " %

%7 The findings showed that inclusion of a bile salt in an emulsion-based bead . )

B formulation of calcitonin improved

of delivery the "

" peptide, calcitonin, across rat

" " the small intestine in vivo. However, as

# " caprate when presented beads, sodium 5 the B

or coco-glucoside were best enhancers G in the rat colon. on the Commenting findings,# % Professor Brayden said, “This study is one of the / of the 0 of first its A 333 kind to explore effects formulation on different components peptide 0' % +" "

intestinal permeability at different of synthesis. stages "

Aguirre, T et al. In vitro and in vivo preclinical evaluation of a minisphere emulsion-based formulation (SmPill ÂŽ) of salmon calcitonin. Eur J Pharm Sci. 2015 Sep 6;79:102111. doi: 10.1016/j.ejps.2015.09.001.

+ B . limited

therapeutic options. This research 64 to treat + " promises a new therapy the " disease. % "

" 23 3 " "

% . " We examined the

effects of the " 00 " (" composition first as " a liquid emulsion and as a solid bead "

and could then " " relate blood levels in rats from

" level calcitonin %

UCD Conway Institute will host a number of new doctoral and postdoctoral researchers thanks to recent EU training network awards involving or being led by Conway Fellows. A

innovative therapeutic strategies for

growing reputation in these emerging

populations.

a blueprint for what biomedical training can look like in future. I am delighted at the potential this programme &0F of

to enable new collaborations, seed new projects % B in personalised and ultimately medicine shape future leaders in this " frontier " research initiative. % 6 "

-

Training future research leaders

the management of chronic vascular " disciplines, UCD is ideally positioned to ' &0F and metabolic diseases affecting ageing put in place a programme that can act as

1 ! 9 7 OPATHY (www.opathy.eu) is a Marie Skłodowska-Curie Innovative Training 5 % Network (ITN) funded under the Horizon @ > ,

2020 Framework Programme. The â‚Ź3M 5 5 programme aims to rapidly and accurately 5 $

diagnose yeast infections by means of innovative will result in &0F ‘omics’ that

improved treatment " strategies.

0 %

These yeasts the " inside of the can + Ccolonise digestive and reproductive without 0 tracts causing harm but become problematic 3 % when the infection is systemic. Under the programme, Conway Fellow, " " Professor Geraldine Butler will *D.GB, supervise two PhD candidates aim to identify 0 % . as they biomarkers can diagnose different that

the stages to enable of infection

" early $ intervention. % EVOLuTION is another Marie " EU Skłodowska-Curie ITN that will provide " training for " 11 young researchers " in

Conway Catherine " Fellow, " Professor Godson is the UCD collaborator in the network that includes %five academic institutions, one SME, six pharmaceutical & " companies as well as and biotechnology partners involved in policy and patents. " "

Professor Orla Feely,. UCD Vice " % President of Research, Innovation & Impact

B" " officially TOPMed10 launched " during the 2015 Conway Festival of Research UCD $ & Innovation. This EU Marie Sklodowska " Curie COFUND international training %

and career development fellowship programme in personalised medicine will $ be led by Institute Director, Professor D.GB Walter Kolch. (" % 4 ("

The â‚Ź2.1M cofunded by the EU, award, " " enables train and" develop a new UCD to

generation scientists clinicians of " and with the interdisciplinary expertise necessary $ % to become leaders in this burgeoning area. . " "

Professor Orla Feely said, " “Given our "

("

#" "

" " " 7 %

. " " 1 " 0 - + " %

? / &0F % B" / (" +% % " Orla F 23 3 Professor Feely, UCD Vice >CC >A President of Research,

Innovation & Impact and Professor Walter Kolch, Director, UCD Conway Institute and Systems Biology Ireland

Significant benefits of weight management drug without diabetes were "

;- 1BK participants randomly allocated either liraglutide

The drug, liraglutide 3.0 mg is beneficial to weight management in obesity when used in combination with diet and increased physical activity according to the findings of an international $ ' study in the New England Journal of Medicine coA A 9 A authored by Conway Fellow, Professor â‚Ź"E+!+00 Carel le Roux. 5 7

Liraglutide is 97% similar to the hormone, < F glucagon-like peptide (GLP-1) in(7 F humans 1' that is released response to food

in 5 intake. 19. Like GLP-1, liraglutide controls food intake 5 $ by increasing feelings of fullness after eating. * % : % ", " " "

In the SCALE™ obesity and prediabetes study, 3731 obese or overweight

3.0 mg or a placebo delivered by injection under the skin once daily for 56 weeks. They were given lifestyle and *+: , advice regularly assessed to evaluate percentage " " +:

the of participants who weight % . lost" experienced change, at least 5% or more than 10% of their initial

" 2A weight. * > " @ " ,

A " # " "

The study showed that liraglutide 3.0 mg, % in combination with diet and increased . -+ activity, + "

physical resulted in significantly greater weight loss than diet and %physical % +

G activity alone. / " " "

Professor le Roux says, “The SCALE™ study has shown that this drug treatment could help patients change the biology that has inhibited their best behavioral efforts. It provides clinicians with evidence of the benefits potential of liraglutide 3.0 mg but +: the also possible side effects to expect. may

While these only occur in a small % . " subset of patients, we need to use this drug and in responsibly a way that minimises " " " risk�.

Reference Xavier Pi-Sunyer et al. A Randomized Trial +: % ; Controlled of 3.0 mg of Liraglutide in Weight Management.NEJM %

I" % B 2015;373(1):11-22| doi:10.1056/NEJMoa1411892

" %

5 ;$

prostate " New molecular target for advanced disease Despite initial G an response, 55 the 8 majority of men with locally advanced

= ! and metastatic cancer = prostate

$ ! progress to develop

8 castrate-resistant ! prostate cancer (CRPC) which, despite 5 the emergence of new treatments, is ! challenging to treat.

5 5 = 5 $

Conway Fellow Professor William Watson and hisG team have identified a promising new molecular target0 " for / + G advanced prostate cancer '

E treatment. . *G0' ., Their research findings, published in the + 1 B B " " scientific journal Prostate, shows that a

protein named serum response factor effective in $ ("

(SRF) is as decreasing cellular as &BD+ proliferation the latest drug in clinical " " % use for advanced disease (MDV3100). 5 The team also demonstrated decreases " " in cellular proliferation in a cellular % / model of advanced disease by using this

" drug (MDV3100) with an SRF inhibitor.

% 4

“We firstly studied the relationship

between SRF and the androgen receptor " " "

(AR), currently

which " is " % the main therapeutic target for advanced prostate + " &BD+ first cancer�, explained Dr Maria Prencipe, " and research

$ author fellow in the Watson group. (" % 0 " " “We went on toG0' . inhibit SRF using

then # siRNA or a small molecule inhibitor and at cellular proliferation looked 4

and apoptosis with the " help of flow $ cytometry. Finally, our in " we validated " (" vitro findings tissues from patients % . in " " with advanced disease�. " %

The team will now begin mechanistic studies on the SRF in advanced . G0' . role of

prostate cancer and test the efficacy of 5 ;$ ;- + ' the inhibitor CCG-1423, alone or in SRF combination with current treatments " " &BD+ (MDV3100) in pre-clinical Should studies. $ this be successful, Dr Prencipe %research . $ hopes it will lead to clinical trials and " potentially a tangible impact on patients " within five years.

. "

Reference ;- + ' " " Prencipe M et al. Relationship between serum response " and " receptor ;- in> 1 cancer. factor androgen prostate B 2015 %Nov;75(15):1704-17. B "

Prostate. doi: 10.1002/ pros.23051. Epub 2015 5 ;$ Aug 7.

?!! % % ?=3=3! 5 ;$

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

SRF protein expression assessed by IHC on clinical tissues from patients with prostate cancer. Examples of negative (0), weak (1), moderate (2) and strong (3) nuclear staining are shown (40X magnifications). G0' . / + G 5 ;$

SPHERE launch welcomed by Minister Varadkar Q

The acronym SPHERE the describes

state-of the art translational interests of

A new UCD-based research group, SPHERE aims to harness unique haematological tools to diagnose and understand a host of inflammatorybased diseases. co-directors < SHERE 1 are Conway Dr Fionnuala NĂ­ Ă inle H Fellows, F and Patricia Maguire.

Dr

8

5 5

The officially launch of SPHERE coincided C with VTE Dublin 2015 conference

the 5 $ that took place at the Croke Park G 2%A Conference Centre on Friday, 18 and Saturday, 19 September "

% 2015. .

Minister for Health, Dr Leo Varadkar T.D. welcomed the launch of SPHERE and spoke the enormous " of " " worldwide burden posed by venous %

thromboembolism during his address to - at international

delegates the" inaugural thrombosis conference, supported by "

" Science Ireland. Foundation "

this group that will focus on ‘Systemic inflammatory disorders: role of blood Haemostatic " and Particles, factors ExtRacEllular

" vesicles’. %

: projects " the Current research investigate of blood "

haemostatic

impact particles, factors and extracellular vesicles in a % wide0 range of diseases including " acute ischaemic stroke, early onset

" " sclerosis, preeclampsia, multiple liver disease, Eisenmenger syndrome " % and schizophrenia. .

+ : 6' " " "

" "

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

" SPHERE, since8 its inception, has attracted funding from industry

significant " % 0 investigator $

collaborators through innovation " granted initiated awards by " $ and Actelion. LEO Pharma %

Pictured (L-R): Dr Fionnuala NĂ­ Ă inle, UCD; Minister for ? Health, Dr Leo Varadkar T.D.; Prof Saskia Middeldorp, B

Centre, " Dr Patricia Academic Medical the Netherlands; Maguire, UCD.

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

Breast cancer research ‘Open House’

+ ;$ and postdoctoral researcher, Dr Susan

On Breast Health Day 2015 (October 15), the Institute marked breast cancer awareness month by hosting an open : 5

= ! house evening for women who have 5

diagnosis, 7 > ? had a cancer their family and friends and coordinated campus @ 5

wide lunchtime events. 8 5 A B/ B. B0,0$ 75

Researchers across 8 5 UCD Conway, 9 ! from 9 5 Systems Biology Ireland (SBI) and the Irish Cancer Society Collaborative Cancer 5 :

55 Research Centre, BREAST-PREDICT

together with 5 worked UCD student societies, One Health and Pharmtox ( :7 > ? $ as well as the patient advocacy group, Europa Donna Ireland and the Plurabelle Paddlers.

During the day, there were opportunities campus-wide to make a positive change for breast health. Event stations provided . fruit B rowing " and free and made machines skipping ropes available for exercising. Volunteers were on hand to provide

"

information and " people share ideas could

" and for change improve " promises to

breast health on social media using+ % 0 " Instagram photo-booths. 1 B 1 85 " F

The evening programme in the Institute " " " allowed participants to hear the latest

research – from breast cancer new % to post-surgical lingerie; therapies visit researchers at the bench in the laboratories or join a rehabilitative exercise class led by specialist instructor

Kennedy (SBI).

" / / " G" / % : + G" ' E - $ $ " F ) " " " %

Students at event station in UCD Student Centre during Breast Health Day 2015

1 " " # "

LabView 360 launch : 5 5

A virtual one of the Institute 8tour

of research laboratories with embedded equipment tutorials been C

! :5 B0,0

has developed by 5 Conway scientist, : ( :-D Dr Gordon Cooke for the institute 9 9 $ intranet through funding provided by B

UCD Teaching and Learning under the SPARC initiative. " " " % . " % . $ " " Conway PhD student, Aoife Murphy

%

Broadcasting science

took part in the 2015 International + + & Rose of 1 Tralee Festival competition " her "

representing native Cork. She J. K " L5C:MJ. K wowed the audience in The Dome as well as the 700,000 television viewers during her stage interview on RTE with presenter, Daithi O Se.

" "

Dr Cooke worked PhD student, Kate " " with Connor % (Gallagher group) and Niall Watts from UCD Media Services to create the virtual tour. Certain items of equipment . " J. K used in " the video demonstrations have QR codes attached that using " can be scanned smartphones and act as a prompt on how + to use the equipment. % &

%

" " J. K " " " Conway PhD student, is co

Jennifer % Cleary . hosting ‘Insiders’, a new 10-part children’s " " * science TV programme on RTE 2 co-funded , "

by Science Foundation Ireland. The first " % episode aired

"

on October 21st and looked

at the science behind sport. Jennifer used a bovine heart to show how the body’s hardest working muscle performs during exercise.

The virtual laboratory tour will be a useful resource for new research staff and students in the early stages of their employment in the Institute by supplementing induction training. It is hoped to expand this pilot initiative to a wider audience and to also include other areas of the institute and other items of equipment.

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

D " + E " " Jennifer is also a final year PhD student

Aoife’s party piece reflected her passion for science communication as she demonstrated a colourful, foaming chemical reaction on stage known as " + " ‘elephant toothpaste’ or the ‘iodine " snake’. / 23 3% .

PhD " " Aoife is a final year student working " Professor

with Conway Fellow, Helen Her Roche. research looks at the impact H and that fatty+ foods have on " obesity inflammation within the body. Professor Roche and many of her team travelled down to Tralee to support Aoife during the competition.

working with Conway Fellow, Professor J. Paul G. Malthouse. Her research uses nuclear reveal magnetic resonance " to the in " which chymotrypsin works to way $ inform how cancer spreads in the body.

B % 1 " B " / . 8

* % 8 I" % daughter L-R Professor Helen Roche and, her Klara, Elaine Kennedy, Ruth Connaughton, 5 8 Marcella O’Reilly, Aoibheann Claire Lyons, Niamh Healy, Aoife * % McMorrow, 8I" % , +

Cooke and Yvonne Lenighan * % I" % , "

" " %

RTE ‘Insider’ hosts: Sarah-Louise Ball, Phil Smyth, Jennifer Cleary

4

1

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

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

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