Four group leaders at the Francis Crick Institute have been awarded European Research Council (ERC) Advanced Grants, each worth between €1.7m and €2.5m. The awards will fund research into cancer, including understanding how obesity drives pancreatic cancer and which mobile parts of the human genome might influence patient response to cancer immunotherapies.
The grants are awarded to outstanding researchers working in EU member states or associated countries. In total, the ERC Advanced Grants for 2020 are worth €507 million and will fund 209 projects involving top researchers in Europe across the humanities, physical and life sciences. The UK will host 13 projects in Life Sciences, and 51 in total across the three fields, the highest number of awards among the eligible countries.
The programme is highly competitive, with the success rate for this round only 8%. The Crick success rate is 57.1%.
Paul Nurse, director of the Crick said: “It’s fantastic to see so many successful UK research teams receiving these highly competitive grants. This highlights the collaborative nature of science and shows that researchers are dedicated to cross-border partnerships. I look forward to seeing this continue through future Horizon Europe funding schemes.”
Olivier Stephan, Head of Pre-award & EU Innovation said: “I am beyond thrilled for Karen, Erik, John and George, whose projects have been selected for funding. I hope this will encourage many scientists at the Crick to keep submitting applications to the ERC as well as engage more widely in all the Horizon Europe funding schemes.”
The four Crick ERC-funded projects
How does obesity drive pancreatic cancer?
Pancreatic cancer is incredibly difficult to treat and only 1% of people diagnosed survive for 10 years or more, so new therapies to treat this disease are urgently needed. Such advances will depend on a better understanding of what drives cancer progression.
Her team will focus on the interactions between fat cells, called adipocytes, and the tumour. They will study metabolic control of the tumour cell environment in animal models and the impact of obesity.
In the future, insights from this project could help provide a basis for the development of new treatments.
Re-organising the structure of tumours
Group leader of the Tumour Cell Biology Laboratory, Erik Sahai, is leading a project (CAN_ORGANISE) which will focus on the spatial and structural organisation of tumours. These architectural patterns hold information about the likely future course of the disease, which is used by doctors to help work out prognosis for patients.
His team will use imaging techniques to analyse these structures, spatial features and patterns. Their aim is to identify mechanisms that control spatial patterns in breast and skin cancer models and use this information to re-organise the spatial architecture of tumours, into patterns that favour effective therapy.
Role of chromatin in DNA replication
Each time a human cell divides, it must make an exact copy of its 46 chromosomes. This requires precise duplication of around six billion DNA base pairs and associated proteins. Mistakes in this process can lead to developmental defects and cancer.
John Diffley, group leader of the Chromosome Replication Laboratory, is heading up a project (MeChroRep) which will study how the disassembly and reassembly of chromatin ensures accurate chromosome duplication during DNA replication.
His team will study yeast and human proteins, to understand the mechanics of the process. The work will underpin the lab’s long-term goal of reconstituting functional chromosomes to understand how DNA replication interacts with gene expression, DNA repair and chromosome segregation.
Identifying new cancer targets by studying endogenous retroelements
Endogenous retroelements (ERE) are genetic parasites that can move around the DNA and amplify their copies, now making up nearly 50% of the human genome. Many have arisen from the integration of viral DNA from retroviruses that infected our ancestors.
Their ability to alter the DNA of the host provides the substrate for the evolution of new genes and new functions that increase the evolutionary fitness of that host. Examples of this are the evolution of antibodies or of the placenta. However, this genetic adaptability that ERE provide can also be exploited by cancer cells to promote cancer progression.
The project, RETROFIT, led by George Kassiotis, group leader of the Retroviral Immunology Laboratory, will focus on the role of EREs in the genetic adaptability and fitness of cancer. Using EREs the lab previously identified in the cancer transcriptome, his team aims to identify which EREs impact cancer initiation, response to immunotherapy and ultimately patient survival.
They will also use information from patient tumour samples, cancer cell lines and mouse models to test their predictions of the function of these EREs. Through this work, they aim to uncover new targets and opportunities for cancer treatment.