Celebrating 10 years of research excellenceOn September 12th 2013, UCD Conway Institute celebrated the 10th anniversary of its official opening with the launch of Igniting Discovery, a publication highlighting the research and innovation achievements of Conway researchers in the past decade.

Over 700 PhD graduates and 350 postdoctoral researchers have been educated and trained to exacting international standards in the past ten years. These highly-skilled individuals have taken up employment in the pharmaceutical, medical device and ICT industries as well as in public agencies and academia, in Ireland and abroad.

The Institute’s research portfolio includes 3,275 peer reviewed research publications with the top 1% published in the most prestigious scientific journals such as Nature, Science and Cell. In addition UCD Conway researchers currently have successful collaborations, leading to publications, with scientists from over 1,500 organisations in 70 countries.

Earlier this year, Conway Fellow, Professor Des Higgins broke the barrier of 100,000 total citations for his work on DNA

sequence comparisons; making him the most highly cited Irish scientist in the past decade and one of the most highly cited scientists worldwide.

The Clustal programme to align protein sequences from the research group of Professor Higgins is just one of a number of exciting innovations that has emerged from the Institute. Since 2003, Conway research-ers have disclosed 108 inventions, filed 139 patents, concluded 21 licence agreements and incorporated 7 UCD spin-out compa-nies from the outputs of Institute research programmes.

Professor Walter Kolch, Director said, “When the Institute was established, its model of multidisciplinary and collabora-tive research was considered a radical vision of how scientific research should be carried out. Today, it is the gold standard.”

Professor Des Fitzgerald, UCD Vice-Presi-dent for Research added, “UCD Conway In-stitute has been a highly effective driver of research productivity and excellence since its establishment. Through its intellectual and infrastructural capabilities, it has risen to the challenge of providing solutions to societal needs in the face of a rapidly

changing economic and research horizon while maintaining research excellence.”

Director’s MessageWelcome!

In the last 3 months, we marked a milestone in the life of the Institute with our 10th anniversary celebrations. This coincided with the 2013 UCD Conway Festival of Research & Innovation and a visit by our distinguished scientific advisory board.

As we enter the next phase in the life of the Institute, we intend continuing to build research excellence and sustain the

vibrant environment that ignites discovery, drives innovation and impacts positively on society for generations.

I extend congratulations to Professor William Gallagher, Director of the first Irish Cancer Society funded Collaborative Cancer Research Centre, BREAST-PREDICT. This funding award is a milestone for cancer research in Ireland that will give new hope to patients and their families. It also highlights our commitment and mission to carry out fundamental research into the

molecular basis of disease.

Following their recent successful applications, I am delighted to welcome a number of new Conway Fellows and their teams whose research programmes will undoubtedly strengthen the research strategy of the Institute into the future.

Professor Walter Kolch Director

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A new European research consortium of industry and academic partners will focus efforts for drug discovery and development of novel eye therapeutics to halt or reverse ocular diseases leading to blindness.

The ‘Drug Discovery & Development of Novel Eye Therapeutics’ (3D-NET) project will be funded through a €1.8 million Marie Curie Industry-Academia Pathways and Partnerships (IAPP) grant award from the EU Framework 7 Programme.

Conway Fellow, Dr Breandan Kennedy will lead and coordinate the consortium

that includes researchers from the University of Valladolid (Spain), KalVista Pharmaceuticals (UK), RenaSci Ltd (UK) and Gadea Grupo Farmacéutico (Spain).

Millions of people worldwide suffer from ocular diseases that deteriorate their quality of life. Conditions such as age-related macular degeneration (AMD) or diabetic retinopathy (DR) are leading causes of irreversible blindness, and are a growing problem as the worldwide population ages.

There is a significant unmet clinical need for more effective treatments to halt

or reverse these ocular diseases. For the first time, the consortium exchanges industry and academic expertise in the development of drugs with potential to treat ocular disease and enhances the capabilities and infrastructure required to test these drugs in relevant pre-clinical models.

The Kennedy laboratory will contribute to the consortium by efficiently screening compounds for effects on ocular angiogenesis and visual function in the zebrafish model and validate ‘hit/lead’ drugs in pre-clinical mouse models of ocular disease.

Developing treatments for irreversible blindness

Welcoming new Conway FellowsProfessor Guenther Eissner served as Senior Vice President and Head of Biolgical Research of the Italian pharmaceutical company Gentium (2004-2007) before being appointed to the Chair for Interdisciplinary Stem Cell Research at the University of Munich. His major research focus is on endothelial pathology in transplant medicine and on mesenchymal stem cells in transplant and regenerative medicine. Prof Eissner is establishing collaborative projects with Conway Fellows on lung-specific endothelial cell biology; mesenchymal stem cells and hypoxia/angiogenesis; endothelium in inflammation and oncology; fibrotide and platelet function.

Prof Guenther Eissner, Professor of Translational Systems Biology, Systems Biology Ireland

Prof Walter Kolch, Director pictured with PhD students (l-r), Anna Sanders, Natalia Volinsky , Paul Lavin and Mattia Bramini

Prof Des Fitzgerald, UCD Vice-President for Research presents the first copy of ‘Igniting Discovery’ to Ms Beatrice Conway, daughter of the Institute namesake, Prof Edward J. Conway FRS

Professor Sabine Koelle graduated in Veterinary Medicine at the University of Munich, Germany, where she also studied medicine and dentistry. She joins UCD from the University of Vienna where she was Head of the Dept of Anatomy, Histology and Embryology. Her research is focused on reproductive medicine, especially on improving the results of assisted reproduction. Prof Koelle hopes to combine modern imaging techniques with molecular analyses in proteomics and genomics to create new diagnostic and therapeutic tools in subfertility and infertility.

Prof Sabine Koelle, Professor of Anatomy & Developmental Biology, UCD School of Medicine and Medical Science

Professor Gerry Wilson joins UCD from the University of Sheffield. A graduate of Medicine from Queen’s University Belfast, he was Professor in Rheumatology and Honorary Consultant Rheumatologist at the University of Sheffield Medical

Prof Gerry Wilson, Arthritis Ireland/UCD Chair of Rheumatology, UCD School of Medicine and Medical Science

Professor Kenneth Wolfe joins UCD from the Smurfit Institute of Genetics, Trinity College Dublin where he was Head of Genetics (2011-13). His research area is genome evolution in eukaryotes with a focus on yeasts as a primary system to work on. Current research projects underway in the Wolfe laboratory are investigating gene gain and loss; orphan genes; gene order evolution; evolution of the yeast MAT locus system.

Prof Kenneth Wolfe, Professor of Genomic Evolution, UCD School of Medicine and Medical Science

Dr Darran O’Connor has successfully built an independent research group within UCD Conway Institute focused on the discovery, validation and mechanistic anchoring of novel cancer biomarkers. Dr O’Connor has a number of funded collaborations with Conway Fellows through the SFI strategic research cluster, Molecular Therapeutics for Cancer Ireland and EU FP7 health programme, AngioPredict.

Dr Darran O’Connor, UCD School of Biomolecular & Biomedical Science

School and Sheffield Teaching Hospitals NHS Foundation Trust. Prof Wilson will be investigating the pathogenesis of inflammatory musculoskeletal diseases. His research interests include the genetic and epigenetic influences in rheumatoid arthritis; ageing and epigenetics; and pharmacogenetics of biological therapies.

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Recent publications from Conway Fellow, Dr Neil Ferguson provide new insights into the structure and thermodynamics of human hepatitis B virus (HBV) replication and show chinks in the armour of HBV that provide new avenues for therapeutic intervention.

Each year, 600,000 people die following infection with this blood-borne virus while 350 million people have chronic HBV infections.

Despite HBV having only four genes, identifying ‘druggable’ targets and developing improved therapies have been hampered by how challenging HBV proteins are to study in vitro.

Dr Ferguson is deconstructing the HBV lifecycle at molecular level to figure out how component parts fit together and facilitate HBV replication within infected liver cells.

Crucial to HBV replication are a series of highly coordinated, molecular self-assembly processes. One key stage is the assembly of a protective protein shell (virus capsid) that envelopes the viral genome. Ferguson’s team have been able to disrupt the sequence of molecular events that make the viral core protein (HBc) form capsids.

Their findings, published in the Proceedings of the National Academy of Sciences, show how subtle thermodynamic tuning of HBc structure, using point mutations or small molecules, can prevent capsid assembly and halt viral replication.

“Capsid formation may be an Achilles’ heel for HBV. If you prevent the protein from assembling, the virus is unable to mature and become infectious”, says Dr Ferguson.

After the capsid forms, it is wrapped in another shell made of viral proteins that help it escape from infected cells. The team showed that preS1, a part of the virion envelope, is another potential therapeutic target. By mimicking its human counterpart, preS1 tricks the host protein export machinery into participating in viral replication but without unduly stressing this machinery to the point of cell death.

This work, the first HBV biomolecular interactions mapped at atomic resolution, provides the structural and thermodynamic roadmap needed to design novel antivirals. Future work aims to therapeutically target preS1 functions without impacting normal hepatocyte functions.

Revealing chinks in the armour of hepatitis B virus

Irish Laboratory Award Finalists Conway researchers are among the finalists in the inaugural Irish Laboratory Awards. The initiative was launched to promote and celebrate the leading people and companies in Irish science.

Over 50,000 people are employed in research and development, production and processing. This industry is now worth 50 billion euro to the economy.

The competitive application process is judged by a panel of experts drawn from across a range of scientific disciplines. Winners will be announced at the gala dinner in the DoubleTree by Hilton Hotel Dublin on December 3rd 2013.

Category finalists: Prof Cormac Taylor (medical laboratory & research laboratory of the year), Dr Alfonso Blanco (education laboratory & laboratory staff member of the year), Dr David Croucher (young leader of the year).

Addressing critical gaps in breast cancer researchBreast cancer will claim more than *185,000 lives by 2030 if 10 critical gaps that exist in breast cancer research are not urgently addressed.

This landmark research, published recently in the international open access journal, Breast Cancer Researchis a unique collaboration of over 100 internationally recognised scientists, clinicians and healthcare professionals from the UK and Ireland.

During 2012, the leading UK research charity, Breast Cancer Campaign, facilitated a series of workshops, each covering a specialty area of breast cancer. Nine expert groups focused on identifying key gaps in their thematic area and detailing how these gaps could be addressed.

Ten priority gaps identified cover areas of genetics, prevention, diagnosis, treatment and support. Five key strategic solutions were also proposed to address these gaps and help treat and support breast cancer patients. These include funding, research infrastructure, multidisciplinary collaborations as well as improved methods of studying the disease and designing clinical trials.

Conway Fellow and Director of the Irish

Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT, Professor William Gallagher who led the working group on Novel Targeted Therapies, Preclinical Research and Biomarkers commented, “Overcoming these gap areas by prioritising this research will reduce over-treatment of breast cancer patients by identifying those who will benefit from chemotherapy or radiotherapy, and improve patient outcomes by tailoring treatment to each individual.”

The UK charity aim to raise £100 million over the next decade to tackle the critical gaps identified. In Ireland, the Irish Cancer Society have similarly committed the proceeds of fundraising, in part due to the Breast Cancer Awareness Month campaign ‘Get the Girls’, to research with the launch of a Collaborative Cancer Research Centre, BREAST-PREDICT in August 2013.

This brings together Ireland’s leading breast cancer researchers with the ultimate goal of achieving tailored treatments for individual patients based on the characteristics of their particular tumour. This personalised medicine approach will improve outcomes for breast cancer patients both in Ireland and worldwide.

Hitting inflammation in the gutsResearchers in UCD Conway Institute and Systems Biology Ireland have identified a way that a new class of anti-inflammatory drugs may be used to treat inflammatory bowel disease (IBD).

IBD describes a group of commonly occurring and severe diseases including Crohn’s disease and ulcerative colitis. Treatment options for the hallmark symptom of chronically inflamed intestinal tissues are limited, often ultimately requiring surgical removal of inflamed tissue.

The team led by Conway Fellow, Professor Cormac Taylor have previously shown that a class of drugs called hydroxylase inhibitors may provide a new approach to the treatment of IBD. This study now outlines how this occurs at the molecular level.

Hypoxia is a key microenvironmental feature of inflamed tissues that strongly impacts on the inflammatory processes. A family of oxygen-sensing enzymes called HIF-hydroxylases are responsible for controlling the cellular adaptive response to hypoxia.

This new study, led by Prof Cormac Taylor, Dr Eoin Cummins and Dr Carsten Scholz and published in the Proceedings of the National Academy of Sciences, show that hydroxylase inhibitors work by blocking a pro-inflammatory pathway termed the IL-1 pathway; a key driver of inflammation.

These results give significant new information as to a new level of crosstalk between hypoxia and inflammation and provide a mechanism to explain how this new approach to the control of

inflammation may work.

“This research stems from studies in our laboratory over the last decade into how cells respond to decreased oxygen levels. We found that cells can adapt to low oxygen levels much like mountain climbers adapt to low oxygen levels at altitude. If we use drugs to mimic this adaptive response in inflammation, it suppresses the inflammatory response” says Taylor.

This collaborative project is supported by Science Foundation Ireland.ReferenceRegulation of IL-1β–induced NF-κB by hydroxylases links key hypoxic and inflammatory signaling pathways. Carsten C. Scholz, Miguel A. S. Cavadas, Murtaza M. Tambuwala, Emily Hams, Javier Rodríguez, Alex von Kriegsheim, Philip Cotter, Ulrike Bruning, Padraic G. Fallon, Alex Cheong, Eoin P. Cummins, and Cormac T. Taylor. PNAS 2013 ; published ahead of print October 21, 2013, doi:10.1073/pnas.1309718110

Pictured (l-r) at the launch of the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT: Mr John McCormack, CEO Irish Cancer Society, Professor John Fitzpatrick, Head of Research, Irish Cancer Society; Sharon Burrell, breast cancer survivor and Professor William Gallagher, Director of the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT

2013 Conway Festival medal for cilia researchDoctoral candidate, Nils Lambacher was awarded the 2013 UCD Conway Festival of Research & Innovation gold medal, sponsored by Cruinn Diagnostics for his research on the regulation of cilium structure in the worm model, Caenorhabditis elegans.

Nils, who is carrying out his studies under the supervision of Conway Fellow, Dr Oliver Blacque, impressed the judging panel with his concise overview of this research project and its innovative potential.

Cilia are present on nearly all of our cells and act like cellular antennae. They play fundamental roles in many motility and sensory functions, including signalling pathways critical to development. Ciliopathies is the collective name for a range of human diseases and syndromes that arise when genetic mutations disrupt the cilium structure and function. One such example is nephronophthisis, the most common cause of kidney failure in children affecting 1 in 50,000 live births in Canada.

The research abstract by Nils Lambacher was one of 30 shortlisted for moderated

2013 Conway Festival medal winner, Nils Lambacher (left) and Prof Des Fitzgerald, UCD Vice-President for Research

presentation from 130 submissions. The other category winners were Crispin Alexander (Ferguson group); Elena Woods (Gautier group); Karolina Weiner-Gorzel (McCann group); Karen Hanrahan (Watson group) and Fiona McGillicuddy (substituted for Orla Finucane).

Delegates at the conference heard plenary lectures from Dr Frank Walsh, CEO, Ossianix; Dr Julian Parkhill, Wellcome Trust Sanger Institute and Professors Cormac Taylor and Des Higgins, UCD. Professor Sir Stephen O’Rahilly, University of Cambridge was awarded the Ulysses medal, UCD’s highest accolade in recognition of his outstanding contribution to research concerning the molecular mechanisms leading to diabetes, obesity and related metabolic and endocrine disorders.

In the innovation session, Dr David O’Connell and Professors Stephen Pennington, William Watson, Fionnuala McAuliffe and Gil Lee described the journeys been undertaken to translate innovative research findings into applications to positively impact society. They discussed challenges faced in commercialising research with the

expert panel, chaired by Mr Brendan Cremen, UCD Director of Enterprise & Commercialisation, including Mr Damian O’Kelly, CEO & Founder Nutritics; Dr Elizabeth Roper, Partner, Rock Spring Ventures; Dr Ruth McMahon, Commercialisation Specialist, Enterprise Ireland and Prof Suzi Jarvis, Co-Director, TCD-UCD Innovation Academy.

The primary sponsors of the 2013 UCD Conway Festival of Research & Innovation were Cruinn Diagnostics Ltd, Bio-Sciences, Roche Diagnostics Ltd and Servier.

Connection between protein folding, allostery & capsid formation.[A]During protein folding, denatured HBc chains[D] associate to form an α-helical, dimeric intermediate[I2]. This intermediate is a structural stepping stone between alternative native dimers: N2ASS (can assemble into capsids) & N2INC (cannot form capsids). Point mutations & small molecules can preferentially stabilise N2INC & ablate capsid formation.[B]Crystal structures of HBc hexamer that corresponds to the 3-fold axis found on capsids (blue/green in [A]) shows HBc has significant structural variation (black arrows) when crystallised under different conditions (blue & magenta).[C]Close up of HBc dimer structure from [B]showing structural variations are propagated throughout the HBc structure, in accord with the structural plasticity found by the Ferguson gp.

ReferencesJürgens MC et al (2013). The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry. Nature Chemical Biology 9,540-547

Alexander CG et al (2013). Thermodynamic origins of protein folding, allostery and capsid formation in the human hepatitis B virus core protein. PNAS USA 110,E2782-2791 (doi:10.1073/pnas.1308846110)

*Projected breast cancer prevalence in the UK in 2030. Maddams J, Utley M, Møller H. Projections of cancer prevalence in the United Kingdom, 2010-2040. British Journal of Cancer 2012; 107: 1195-1202.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research 2013, 15: R92 doi:10.1186/bcr3493

€

Recent publications from Conway Fellow, Dr Neil Ferguson provide new insights into the structure and thermodynamics of human hepatitis B virus (HBV) replication and show chinks in the armour of HBV that provide new avenues for therapeutic intervention.

Each year, 600,000 people die following infection with this blood-borne virus while 350 million people have chronic HBV infections.

Despite HBV having only four genes, identifying ‘druggable’ targets and developing improved therapies have been hampered by how challenging HBV proteins are to study in vitro.

Dr Ferguson is deconstructing the HBV lifecycle at molecular level to figure out how component parts fit together and facilitate HBV replication within infected liver cells.

Crucial to HBV replication are a series of highly coordinated, molecular self-assembly processes. One key stage is the assembly of a protective protein shell (virus capsid) that envelopes the viral genome. Ferguson’s team have been able to disrupt the sequence of molecular events that make the viral core protein (HBc) form capsids.

Their findings, published in the Proceedings of the National Academy of Sciences, show how subtle thermodynamic tuning of HBc structure, using point mutations or small molecules, can prevent capsid assembly and halt viral replication.

“Capsid formation may be an Achilles’ heel for HBV. If you prevent the protein from assembling, the virus is unable to mature and become infectious”, says Dr Ferguson.

After the capsid forms, it is wrapped in another shell made of viral proteins that help it escape from infected cells. The team showed that preS1, a part of the virion envelope, is another potential therapeutic target. By mimicking its human counterpart, preS1 tricks the host protein export machinery into participating in viral replication but without unduly stressing this machinery to the point of cell death.

This work, the first HBV biomolecular interactions mapped at atomic resolution, provides the structural and thermodynamic roadmap needed to design novel antivirals. Future work aims to therapeutically target preS1 functions without impacting normal hepatocyte functions.

Revealing chinks in the armour of hepatitis B virus

Irish Laboratory Award Finalists Conway researchers are among the finalists in the inaugural Irish Laboratory Awards. The initiative was launched to promote and celebrate the leading people and companies in Irish science.

Over 50,000 people are employed in research and development, production and processing. This industry is now worth 50 billion euro to the economy.

The competitive application process is judged by a panel of experts drawn from across a range of scientific disciplines. Winners will be announced at the gala dinner in the DoubleTree by Hilton Hotel Dublin on December 3rd 2013.

Category finalists: Prof Cormac Taylor (medical laboratory & research laboratory of the year), Dr Alfonso Blanco (education laboratory & laboratory staff member of the year), Dr David Croucher (young leader of the year).

Addressing critical gaps in breast cancer researchBreast cancer will claim more than *185,000 lives by 2030 if 10 critical gaps that exist in breast cancer research are not urgently addressed.

This landmark research, published recently in the international open access journal, Breast Cancer Researchis a unique collaboration of over 100 internationally recognised scientists, clinicians and healthcare professionals from the UK and Ireland.

During 2012, the leading UK research charity, Breast Cancer Campaign, facilitated a series of workshops, each covering a specialty area of breast cancer. Nine expert groups focused on identifying key gaps in their thematic area and detailing how these gaps could be addressed.

Ten priority gaps identified cover areas of genetics, prevention, diagnosis, treatment and support. Five key strategic solutions were also proposed to address these gaps and help treat and support breast cancer patients. These include funding, research infrastructure, multidisciplinary collaborations as well as improved methods of studying the disease and designing clinical trials.

Conway Fellow and Director of the Irish

Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT, Professor William Gallagher who led the working group on Novel Targeted Therapies, Preclinical Research and Biomarkers commented, “Overcoming these gap areas by prioritising this research will reduce over-treatment of breast cancer patients by identifying those who will benefit from chemotherapy or radiotherapy, and improve patient outcomes by tailoring treatment to each individual.”

The UK charity aim to raise £100 million over the next decade to tackle the critical gaps identified. In Ireland, the Irish Cancer Society have similarly committed the proceeds of fundraising, in part due to the Breast Cancer Awareness Month campaign ‘Get the Girls’, to research with the launch of a Collaborative Cancer Research Centre, BREAST-PREDICT in August 2013.

This brings together Ireland’s leading breast cancer researchers with the ultimate goal of achieving tailored treatments for individual patients based on the characteristics of their particular tumour. This personalised medicine approach will improve outcomes for breast cancer patients both in Ireland and worldwide.

Hitting inflammation in the gutsResearchers in UCD Conway Institute and Systems Biology Ireland have identified a way that a new class of anti-inflammatory drugs may be used to treat inflammatory bowel disease (IBD).

IBD describes a group of commonly occurring and severe diseases including Crohn’s disease and ulcerative colitis. Treatment options for the hallmark symptom of chronically inflamed intestinal tissues are limited, often ultimately requiring surgical removal of inflamed tissue.

The team led by Conway Fellow, Professor Cormac Taylor have previously shown that a class of drugs called hydroxylase inhibitors may provide a new approach to the treatment of IBD. This study now outlines how this occurs at the molecular level.

Hypoxia is a key microenvironmental feature of inflamed tissues that strongly impacts on the inflammatory processes. A family of oxygen-sensing enzymes called HIF-hydroxylases are responsible for controlling the cellular adaptive response to hypoxia.

This new study, led by Prof Cormac Taylor, Dr Eoin Cummins and Dr Carsten Scholz and published in the Proceedings of the National Academy of Sciences, show that hydroxylase inhibitors work by blocking a pro-inflammatory pathway termed the IL-1 pathway; a key driver of inflammation.

These results give significant new information as to a new level of crosstalk between hypoxia and inflammation and provide a mechanism to explain how this new approach to the control of

inflammation may work.

“This research stems from studies in our laboratory over the last decade into how cells respond to decreased oxygen levels. We found that cells can adapt to low oxygen levels much like mountain climbers adapt to low oxygen levels at altitude. If we use drugs to mimic this adaptive response in inflammation, it suppresses the inflammatory response” says Taylor.

This collaborative project is supported by Science Foundation Ireland.ReferenceRegulation of IL-1β–induced NF-κB by hydroxylases links key hypoxic and inflammatory signaling pathways. Carsten C. Scholz, Miguel A. S. Cavadas, Murtaza M. Tambuwala, Emily Hams, Javier Rodríguez, Alex von Kriegsheim, Philip Cotter, Ulrike Bruning, Padraic G. Fallon, Alex Cheong, Eoin P. Cummins, and Cormac T. Taylor. PNAS 2013 ; published ahead of print October 21, 2013, doi:10.1073/pnas.1309718110

Pictured (l-r) at the launch of the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT: Mr John McCormack, CEO Irish Cancer Society, Professor John Fitzpatrick, Head of Research, Irish Cancer Society; Sharon Burrell, breast cancer survivor and Professor William Gallagher, Director of the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT

2013 Conway Festival medal for cilia researchDoctoral candidate, Nils Lambacher was awarded the 2013 UCD Conway Festival of Research & Innovation gold medal, sponsored by Cruinn Diagnostics for his research on the regulation of cilium structure in the worm model, Caenorhabditis elegans.

Nils, who is carrying out his studies under the supervision of Conway Fellow, Dr Oliver Blacque, impressed the judging panel with his concise overview of this research project and its innovative potential.

Cilia are present on nearly all of our cells and act like cellular antennae. They play fundamental roles in many motility and sensory functions, including signalling pathways critical to development. Ciliopathies is the collective name for a range of human diseases and syndromes that arise when genetic mutations disrupt the cilium structure and function. One such example is nephronophthisis, the most common cause of kidney failure in children affecting 1 in 50,000 live births in Canada.

The research abstract by Nils Lambacher was one of 30 shortlisted for moderated

2013 Conway Festival medal winner, Nils Lambacher (left) and Prof Des Fitzgerald, UCD Vice-President for Research

presentation from 130 submissions. The other category winners were Crispin Alexander (Ferguson group); Elena Woods (Gautier group); Karolina Weiner-Gorzel (McCann group); Karen Hanrahan (Watson group) and Fiona McGillicuddy (substituted for Orla Finucane).

Delegates at the conference heard plenary lectures from Dr Frank Walsh, CEO, Ossianix; Dr Julian Parkhill, Wellcome Trust Sanger Institute and Professors Cormac Taylor and Des Higgins, UCD. Professor Sir Stephen O’Rahilly, University of Cambridge was awarded the Ulysses medal, UCD’s highest accolade in recognition of his outstanding contribution to research concerning the molecular mechanisms leading to diabetes, obesity and related metabolic and endocrine disorders.

In the innovation session, Dr David O’Connell and Professors Stephen Pennington, William Watson, Fionnuala McAuliffe and Gil Lee described the journeys been undertaken to translate innovative research findings into applications to positively impact society. They discussed challenges faced in commercialising research with the

expert panel, chaired by Mr Brendan Cremen, UCD Director of Enterprise & Commercialisation, including Mr Damian O’Kelly, CEO & Founder Nutritics; Dr Elizabeth Roper, Partner, Rock Spring Ventures; Dr Ruth McMahon, Commercialisation Specialist, Enterprise Ireland and Prof Suzi Jarvis, Co-Director, TCD-UCD Innovation Academy.

The primary sponsors of the 2013 UCD Conway Festival of Research & Innovation were Cruinn Diagnostics Ltd, Bio-Sciences, Roche Diagnostics Ltd and Servier.

Connection between protein folding, allostery & capsid formation.[A]During protein folding, denatured HBc chains[D] associate to form an α-helical, dimeric intermediate[I2]. This intermediate is a structural stepping stone between alternative native dimers: N2ASS (can assemble into capsids) & N2INC (cannot form capsids). Point mutations & small molecules can preferentially stabilise N2INC & ablate capsid formation.[B]Crystal structures of HBc hexamer that corresponds to the 3-fold axis found on capsids (blue/green in [A]) shows HBc has significant structural variation (black arrows) when crystallised under different conditions (blue & magenta).[C]Close up of HBc dimer structure from [B]showing structural variations are propagated throughout the HBc structure, in accord with the structural plasticity found by the Ferguson gp.

ReferencesJürgens MC et al (2013). The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry. Nature Chemical Biology 9,540-547

Alexander CG et al (2013). Thermodynamic origins of protein folding, allostery and capsid formation in the human hepatitis B virus core protein. PNAS USA 110,E2782-2791 (doi:10.1073/pnas.1308846110)

*Projected breast cancer prevalence in the UK in 2030. Maddams J, Utley M, Møller H. Projections of cancer prevalence in the United Kingdom, 2010-2040. British Journal of Cancer 2012; 107: 1195-1202.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research 2013, 15: R92 doi:10.1186/bcr3493

Celebrating 10 years of research excellenceOn September 12th 2013, UCD Conway Institute celebrated the 10th anniversary of its official opening with the launch of Igniting Discovery, a publication highlighting the research and innovation achievements of Conway researchers in the past decade.

Over 700 PhD graduates and 350 postdoctoral researchers have been educated and trained to exacting international standards in the past ten years. These highly-skilled individuals have taken up employment in the pharmaceutical, medical device and ICT industries as well as in public agencies and academia, in Ireland and abroad.

The Institute’s research portfolio includes 3,275 peer reviewed research publications with the top 1% published in the most prestigious scientific journals such as Nature, Science and Cell. In addition UCD Conway researchers currently have successful collaborations, leading to publications, with scientists from over 1,500 organisations in 70 countries.

Earlier this year, Conway Fellow, Professor Des Higgins broke the barrier of 100,000 total citations for his work on DNA

sequence comparisons; making him the most highly cited Irish scientist in the past decade and one of the most highly cited scientists worldwide.

The Clustal programme to align protein sequences from the research group of Professor Higgins is just one of a number of exciting innovations that has emerged from the Institute. Since 2003, Conway research-ers have disclosed 108 inventions, filed 139 patents, concluded 21 licence agreements and incorporated 7 UCD spin-out compa-nies from the outputs of Institute research programmes.

Professor Walter Kolch, Director said, “When the Institute was established, its model of multidisciplinary and collabora-tive research was considered a radical vision of how scientific research should be carried out. Today, it is the gold standard.”

Professor Des Fitzgerald, UCD Vice-Presi-dent for Research added, “UCD Conway In-stitute has been a highly effective driver of research productivity and excellence since its establishment. Through its intellectual and infrastructural capabilities, it has risen to the challenge of providing solutions to societal needs in the face of a rapidly

changing economic and research horizon while maintaining research excellence.”

Director’s MessageWelcome!

In the last 3 months, we marked a milestone in the life of the Institute with our 10th anniversary celebrations. This coincided with the 2013 UCD Conway Festival of Research & Innovation and a visit by our distinguished scientific advisory board.

As we enter the next phase in the life of the Institute, we intend continuing to build research excellence and sustain the

vibrant environment that ignites discovery, drives innovation and impacts positively on society for generations.

I extend congratulations to Professor William Gallagher, Director of the first Irish Cancer Society funded Collaborative Cancer Research Centre, BREAST-PREDICT. This funding award is a milestone for cancer research in Ireland that will give new hope to patients and their families. It also highlights our commitment and mission to carry out fundamental research into the

molecular basis of disease.

Following their recent successful applications, I am delighted to welcome a number of new Conway Fellows and their teams whose research programmes will undoubtedly strengthen the research strategy of the Institute into the future.

Professor Walter Kolch Director

Issu

e 20

, Win

ter 2

013

A new European research consortium of industry and academic partners will focus efforts for drug discovery and development of novel eye therapeutics to halt or reverse ocular diseases leading to blindness.

The ‘Drug Discovery & Development of Novel Eye Therapeutics’ (3D-NET) project will be funded through a €1.8 million Marie Curie Industry-Academia Pathways and Partnerships (IAPP) grant award from the EU Framework 7 Programme.

Conway Fellow, Dr Breandan Kennedy will lead and coordinate the consortium

that includes researchers from the University of Valladolid (Spain), KalVista Pharmaceuticals (UK), RenaSci Ltd (UK) and Gadea Grupo Farmacéutico (Spain).

Millions of people worldwide suffer from ocular diseases that deteriorate their quality of life. Conditions such as age-related macular degeneration (AMD) or diabetic retinopathy (DR) are leading causes of irreversible blindness, and are a growing problem as the worldwide population ages.

There is a significant unmet clinical need for more effective treatments to halt

or reverse these ocular diseases. For the first time, the consortium exchanges industry and academic expertise in the development of drugs with potential to treat ocular disease and enhances the capabilities and infrastructure required to test these drugs in relevant pre-clinical models.

The Kennedy laboratory will contribute to the consortium by efficiently screening compounds for effects on ocular angiogenesis and visual function in the zebrafish model and validate ‘hit/lead’ drugs in pre-clinical mouse models of ocular disease.

Developing treatments for irreversible blindness

Welcoming new Conway FellowsProfessor Guenther Eissner served as Senior Vice President and Head of Biolgical Research of the Italian pharmaceutical company Gentium (2004-2007) before being appointed to the Chair for Interdisciplinary Stem Cell Research at the University of Munich. His major research focus is on endothelial pathology in transplant medicine and on mesenchymal stem cells in transplant and regenerative medicine. Prof Eissner is establishing collaborative projects with Conway Fellows on lung-specific endothelial cell biology; mesenchymal stem cells and hypoxia/angiogenesis; endothelium in inflammation and oncology; fibrotide and platelet function.

Prof Guenther Eissner, Professor of Translational Systems Biology, Systems Biology Ireland

Prof Walter Kolch, Director pictured with PhD students (l-r), Anna Sanders, Natalia Volinsky , Paul Lavin and Mattia Bramini

Prof Des Fitzgerald, UCD Vice-President for Research presents the first copy of ‘Igniting Discovery’ to Ms Beatrice Conway, daughter of the Institute namesake, Prof Edward J. Conway FRS

Professor Sabine Koelle graduated in Veterinary Medicine at the University of Munich, Germany, where she also studied medicine and dentistry. She joins UCD from the University of Vienna where she was Head of the Dept of Anatomy, Histology and Embryology. Her research is focused on reproductive medicine, especially on improving the results of assisted reproduction. Prof Koelle hopes to combine modern imaging techniques with molecular analyses in proteomics and genomics to create new diagnostic and therapeutic tools in subfertility and infertility.

Prof Sabine Koelle, Professor of Anatomy & Developmental Biology, UCD School of Medicine and Medical Science

Professor Gerry Wilson joins UCD from the University of Sheffield. A graduate of Medicine from Queen’s University Belfast, he was Professor in Rheumatology and Honorary Consultant Rheumatologist at the University of Sheffield Medical

Prof Gerry Wilson, Arthritis Ireland/UCD Chair of Rheumatology, UCD School of Medicine and Medical Science

Professor Kenneth Wolfe joins UCD from the Smurfit Institute of Genetics, Trinity College Dublin where he was Head of Genetics (2011-13). His research area is genome evolution in eukaryotes with a focus on yeasts as a primary system to work on. Current research projects underway in the Wolfe laboratory are investigating gene gain and loss; orphan genes; gene order evolution; evolution of the yeast MAT locus system.

Prof Kenneth Wolfe, Professor of Genomic Evolution, UCD School of Medicine and Medical Science

Dr Darran O’Connor has successfully built an independent research group within UCD Conway Institute focused on the discovery, validation and mechanistic anchoring of novel cancer biomarkers. Dr O’Connor has a number of funded collaborations with Conway Fellows through the SFI strategic research cluster, Molecular Therapeutics for Cancer Ireland and EU FP7 health programme, AngioPredict.

Dr Darran O’Connor, UCD School of Biomolecular & Biomedical Science

School and Sheffield Teaching Hospitals NHS Foundation Trust. Prof Wilson will be investigating the pathogenesis of inflammatory musculoskeletal diseases. His research interests include the genetic and epigenetic influences in rheumatoid arthritis; ageing and epigenetics; and pharmacogenetics of biological therapies.