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MicroC SIGNED

Agent-Based Modelling of Gene Networks to model clonal selection in the tumour microenvironment and predict therapeutic resistance

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EC-Contrib. €

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Project "MicroC" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

Organization address
address: WELLINGTON SQUARE UNIVERSITY OFFICES
city: OXFORD
postcode: OX1 2JD
website: www.ox.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙996˙325 €
 EC max contribution 1˙996˙325 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-06-01   to  2023-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) coordinator 1˙996˙325.00

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 Project objective

The occurrence of therapeutic resistance is a major cause for the small effect on overall survival showed by targeted cancer therapies. Whilst experimental strategies to evaluate available treatments have been faced by an ever increasing number of possible combinations, computational approaches have been challenged by the lack of a framework able to model the multiple interactions encompassed by the three major factors affecting therapeutic resistance: selection of resistant clones, adaptability of gene signalling networks, and a protective and hypoxic tumour microenvironment.

Here I propose a novel modelling framework, Agent-Based Modelling of Gene Networks, which brings together powerful computational modelling techniques and gene networks. This combination allows biological hypotheses to be tested in a controlled stepwise fashion, and it lends itself naturally to model a heterogeneous population of cells acting and evolving in a dynamic microenvironment, which is needed to predict therapeutic resistance and guide effective treatment selection.

Using triple negative breast cancer (TNBC) as a testing case (15% of breast cancers, lacks validated), I propose to:

1. Develop a computational model of the TNBC tumour microenvironment using in-vitro and in-vivo, including patient-derived, models and data from clinical samples. 2. Validate the ability of the model to predict driver genes conferring a survival advantage to cancer cells in a hypoxic microenvironment. 3. Predict combinations of druggable targets to tackle TNBC therapeutic resistance. 4. Select most effective drug combinations and validate pre-clinically.

This project will deliver pre-clinically validated drug combinations, new therapeutic targets and a virtual environment to study individual tumours and predict therapeutic resistance. Complementing and empowering experimental models and assays, microC will offer a new powerful tool for diagnosis and therapy.

 Publications

year authors and title journal last update
List of publications.
2020 Simon R. Lord, Jennifer M. Collins, Wei-Chen Cheng, Syed Haider, Simon Wigfield, Edoardo Gaude, Barbara A. Fielding, Katherine E. Pinnick, Ulrike Harjes, Ashvina Segaran, Pooja Jha, Gerald Hoefler, Michael N. Pollak, Alastair M. Thompson, Pankaj G. Roy, Ruth. English, Rosie F. Adams, Christian Frezza, Francesca M. Buffa, Fredrik Karpe, Adrian L. Harris
Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin
published pages: 258-265, ISSN: 0007-0920, DOI: 10.1038/s41416-019-0665-5
British Journal of Cancer 122/2 2020-02-05
2019 Dimitrios Voukantsis, Kenneth Kahn, Martin Hadley, Rowan Wilson, Francesca M Buffa
Modeling genotypes in their microenvironment to predict single- and multi-cellular behavior
published pages: , ISSN: 2047-217X, DOI: 10.1093/gigascience/giz010
GigaScience 8/3 2020-02-05
2018 Simon R. Lord, Wei-Chen Cheng, Dan Liu, Edoardo Gaude, Syed Haider, Tom Metcalf, Neel Patel, Eugene J. Teoh, Fergus Gleeson, Kevin Bradley, Simon Wigfield, Christos Zois, Daniel R. McGowan, Mei-Lin Ah-See, Alastair M. Thompson, Anand Sharma, Luc Bidaut, Michael Pollak, Pankaj G. Roy, Fredrik Karpe, Tim James, Ruth English, Rosie F. Adams, Leticia Campo, Lisa Ayers, Cameron Snell, Ioannis Roxanis,
Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer
published pages: 679-688.e4, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.08.021
Cell Metabolism 28/5 2020-02-05
2018 Andrew Dhawan, Jacob G. Scott, Adrian L. Harris, Francesca M. Buffa
Pan-cancer characterisation of microRNA across cancer hallmarks reveals microRNA-mediated downregulation of tumour suppressors
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07657-1
Nature Communications 9/1 2020-02-05

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The information about "MICROC" are provided by the European Opendata Portal: CORDIS opendata.

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