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GlaxoSmithKline (GSK) has issued a call for proposals for collaborative research in Functional Genomics (FxG)1 including Synthetic Lethality2 linked to GSK strategic priorities and leveraging key UK Life Sciences Infrastructure.

GSK logoGSK are seeking ambitious ideas that can transform their understanding of how genetics influences disease and enable the identification of novel and high quality genetically validated targets. This call aims to enable GSK to build relationships and capability in this area with a view to determining where to focus their UK FxG investments in the longer term.

GSK is strengthening its pipeline through a focus on oncology and immunology underpinned by significant investments in human genetics (e.g. 23andMe), advanced functional genomics technologies and Artificial Intelligence/Machine Learning (AI/ML – see www.gsk.ai) to help identify the most promising new medicines.

To maximise the probability of success of their genetics- and genomics-informed oncology and immunology-centred R&D strategy, GSK have a strategic focus on increasing the depth and breadth of understanding of cancer and immune biology as it relates to normal physiology, disease mechanisms, response to infection and potential therapeutic approaches. The success of this strategy will be enabled in part by collaborations with trusted clinical and academic collaborators, selected based on world-class expertise and access to high-quality relevant patient samples.

Note: Applicants must demonstrate how proposed projects will leverage key UK Life Sciences Infrastructure to maximise potential research impact for patients. See accompanying video for further information.

UK Life Sciences Infrastructure includes for example the UK Biobank, NIHR-Bioresource, HDR-UK Digital Innovation Hubs and Genomics England 100K Genomes Project (see 2020 LSIS update). GSK has provided support and investment to establish this infrastructure and is keen to leverage this investment.

GSK is looking to build on its internal capabilities and existing partnerships by establishing programmes of research associated with four key areas:

  1. Patient centric research - Linking genomic variants to cell-specific function and disease mechanisms requires comprehensive analysis of genome regulation across a range of cell types and tissues from large numbers of patients. Access to appropriate cellular resources (primary cells, IPS capabilities and organoids) is a core requirement of a successful FxG campaign. Such resources may include primary cells or patient-derived iPSCs, organoids from both “healthy” individuals and patients at key disease stages (e.g. IBD flare). These should be linked to longitudinal medical records.
  2. Technologies enabling further understanding of molecular phenotype - There is no shortage of common variants associated with a wide number of different diseases.  The real obstacle is turning this information into a better understanding of mechanisms that might be targeted to provide therapeutic benefit. GSK are seeking unbiased novel approaches in order to perform deep molecular profiling e.g. single cell multi-‘omics/cellular fingerprinting methodologies to translate information on genetic variants into insights into gene regulation and disease.
  3. Technologies associated with perturbation – The ability to intervene/perturb cellular systems via an increasing range of gene editing technologies and to measure the consequences via the application of bespoke functional readouts allows GSK to identify targets based on screening for disease relevant phenotypes and to validate mechanistic hypotheses. 
  4. Best in class data analysis capabilities – FxG approaches generate huge and complex data sets creating a need for reliable data science infrastructure to enable data interrogation using advanced analytics such as AI/ML. Seamless wet-dry lab integration is highly desirable to maximise value.

Background

1Functional Genomics comprises a set of technologies and analytical methods used to measure and perturb at scale to determine the function of genes and genomes. At GSK, these technologies are especially applied to the understanding of human disease mechanisms and the identification of novel high quality and genetically validated targets.

Many genetic signals (~80%) from genetic studies such as GWAS, map to non-coding regions of the genome, presenting challenges in linking common and rare variants to the causal disease gene and ultimately to a function (the so-called variant to function (V2F) challenge). This makes it difficult to confirm potential new drug targets, slowing down the development of effective therapies and reducing the number of successful clinical trials.

2Synthetic lethality describes a concept of context restricted gene essentiality that has been used, for example, to identify novel tumour cell specific therapeutic targets in oncology (Behan, F.M. et al., Nature 568, 511–516 (2019)). The historical lack of scalable methods to probe gene function has left this a relatively untapped space. Rapid recent advances in functional genomic technologies and complex disease models have created significant opportunities for target discovery of synthetic lethal targets or more broadly to run gene modifier large scale screens.

  • This call is open to group leaders from the University of Oxford
  • Funding will be provided for a two-year post-doctoral post and appropriate PI time, plus reasonable consumables. There may be an opportunity to extend the post depending on project outcomes.
  • Multi-disciplinary bids involving more than one academic group would be welcomed.
  • Proposals do not need to be fully defined at the expression of interest stage – ideas that are of interest to GSK can be further developed at the second stage of the call. 

In the video below, Tony Wood (SVP Medicinal Science and Technology, GSK R&D) discusses the importance of identification of genetically validated targets, recent investments and why this call is being launched as part of GSK’s strategy.

 Interview transcript

 

  • Applicants should read the call document for further information about the call
  • Please complete the short non-confidential Expression of Interest Form and submit to Charlotte Bell, Business Partnerships Manager, by Friday 28 August 2020.
  • We are encouraging applications to come in throughout July and August so that interested academics can have conversations with GSK discuss potential proposals and seek feedback.
  • Note that proposals do not need to be fully defined at the Expression of Interest stage – ideas that are of interest can be further developed during the second stage of the call. All applications will be reviewed and shortlisted by a GSK expert panel.
  • Prior to submitting your Expression of Interest form, please discuss any issues related to potential IP/freedom to operate restrictions with Charlotte Bell.
  • Shortlisted applicants will be informed by Friday 14 September 2020 at the latest and will be partnered with a GSK scientist to further develop the proposal for presentation to the Joint Steering Committee in late September (Date TBC).
  • Please refer to the Frequently Asked Questions (FAQ) document

Call opens (Expressions of Interest stage)

We are encouraging applications to come in throughout July and August so that interested academics can have conversations with GSK to discuss potential proposals and seek feedback.

 Monday 6 July

Call closes (Expressions of Interest stage) Friday 28 August, 5pm
Shortlisting completed by GSK

Applicants informed of shortlisting outcome

Those who are invited to the second stage are then connected with GSK scientists to work up a proposal in the form of a presentation to be made at the Oxford-GSK Joint Steering Committee.

Monday 14 September
Oxford-GSK Joint Steering Committee Meeting Meeting
Applicants invited to a time slot within the meeting to give a 10-15 minute presentation, jointly with the GSK scientist, and field questions from the committee
Friday 9 October (between 10-12.30)
Applicants informed of final outcomes Mid-October
Finalisation of workplan/budget and commencement of contracting process From October (aimed for completion in December)
Projects start January 2021

For all enquiries please contact Charlotte Bell, Business Partnerships Manager, Medical Sciences Business Partnerships Office.

Charlotte can connect you to GSK for further information and discussion of your ideas.

Email: charlotte.bell@medsci.ox.ac.uk

Telephone: 01865 289877

GSK Representatives

Tony Wood, SVP, Head of Medicinal Science and Technologies (MST)

Euan Stronach, Senior Director, Functional Genomics, Global Gene Editing & Genetic Screening, MST

Chun-Fang Xu, Senior Director, Human Genetics, Research

Gillian Tannahill, Scientific Director, Immunology Network, Research

Victoria Higgins, Senior Director, UK Academic Alliance Management (Alliance Director/Secretariat/Business Lead)

Oxford Representatives

Chas Bountra, Pro Vice-Chancellor for Innovation (Chair)

Kay Davies, Professor of Genetics, Department of Physiology, Anatomy and Genetics

John Todd, Professor of Precision Medicine at the University of Oxford, Director of the Wellcome Centre for Human Genetics

Jenny Taylor, Professor, Programme Director, Genomic Medicine Theme NIHR Oxford BRC 

David Clifton, Professor of Clinical Machine Learning, Department of Engineering Science

Charlotte Bell, Business Partnerships Manager (Alliance Management/Secretariat)

Duncan Richards, Climax Professor of Clinical Therapeutics and Director of OCTRU (observer)

Maxine Allen, Director of the Business Partnerships Office (observer)