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08.02.18 Two projects on the CRUK Grand Challenge shortlist feature Gurdon Institute scientists

last modified Feb 08, 2018 08:25 AM
Gurdon Institute researchers are part of two international teams whose projects have been selected onto the shortlist for CRUK's biggest research grants of £20 million, the 'Grand Challenge'

Both projects were proposed in response to the same challenge of eight that were set by an expert panel: 

"Determine the mechanisms that cause cancer without known mutagenesis, such as obesity, in order to devise novel interventions."

Investigation of the role of inflammation in cancer

Two University of Cambridge scientists, Professor Steve Jackson of the Wellcome Trust/ Cancer Research UK Gurdon Institute and Dr John Perry of the MRC Epidemiology Unit, are members of a multi-disciplinary team of scientists which has been shortlisted to the final stages of Cancer Research UK's Grand Challenge -  an ambitious series of £20m global grants tackling some of the toughest questions in cancer research. The team also includes researchers from the University of Pennsylvania, The Francis Crick Institute, and the University of California, San Francisco, and is led by Professor Rong Li of Johns Hopkins University School of Medicine.

The Grand Challenge award aims to revolutionise how we diagnose, prevent and treat cancer by providing international multi-disciplinary teams the freedom to try novel approaches, at scale, in the pursuit of life-changing discoveries. The team will now receive seed-funding of up to £30,000 to draft their full research proposal, and the winning proposal will be announced in autumn 2018.

The proposed research project seeks to understand how chronic inflammation contributes to the development of cancers, focusing initially on chronic inflammation and colitis in inflammatory bowel disease, which are known risk factors for colorectal cancer.

The team hypothesise that stress and damage to cells of the intestinal mucosa due to inflammation elevates chromosomal instability. Chromosomal instability, where either whole chromosomes or parts of chromosomes are duplicated or deleted, is found in over 80% of cases of both inflammatory bowel disease and colorectal cancer. By unravelling the molecular mechanisms involved in these processes using innovative genomic analysis and cell-based studies, mouse models of disease and human clinical samples, they hope to speed up the identification of new ways to diagnose and prevent these diseases, and to develop new therapies.

Dr John Perry of the MRC Epidemiology Unit at the University of Cambridge, who will be undertaking an analysis of alterations in gene and chromosome structure in over 1 million individuals as part of this project, said:

“I’m excited to be part of a multi-disciplinary team using state-of-the-art experimental approaches to answer basic questions in cancer biology. Understanding how inflammation leads to errors in cell division has the potential to identify new pathways to target for future therapies.”

Professor Steve Jackson of The Gurdon Institute at the University of Cambridge, who will explore, in mouse models of inflammatory bowel disease, how their discoveries about chromosomal instability can be used to treat cancer, said: "I am delighted that our application has made the shortlist and hope that we are successful at the next stage!".

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Getting the FACTS on how obesity causes cancer

Gurdon Institute group leader Meritxell Huch is lead Principal Investigator on a project that will explore the relationship between fat accumulation and cancer in the liver and other tissues, should it be successful in winning Cancer Research UK's Grand Challenge funding of £20 million.

Research has shown that many types of cancer are more common in people who are overweight or obese, including liver cancer, breast cancer and bowel cancer. But it is not clear exactly how excess fat causes cancer. As obesity is linked to 13 different types of cancer, it’s crucial that we gain knowledge in this area.

Dr Huch has pioneered the production of liver organoids as an in vitro model that offers an expandable source of tissue for investigating health, regeneration and disease.  She has gathered a world-renowned experts from the UK, The Netherlands, France, Austria and the US to work on the project, including Gurdon Institute group leader Tony Kouzarides and associate group leader Ben Simons.

Dr Huch said: "We are delighted to learn that CRUK has shortlisted our project on Fat Accumulation and Cancer causes: mechanistic insighTS in disease development (FACTS). By bringing together a team of clinicians and experts in organoid culture technology, mouse and human genetics and epigenetics, computational biology and genetic engineering, we propose to target the mechanisms by which fat accumulation leads to cancer predisposition, with special attention to liver, colon and breast tumours."

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All shortlisted projects will receive funding to support preparation of a more detailed research proposal, and the final winner of the Grand Challenge jackpot will be announced in autumn 2018.

 

Read more about research in the Jackson lab and watch Steve describe his work on video.

Read more about research in the Huch lab and watch Meri describe her work on video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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