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Antimicrobial Target Discovery and Validation

 

Summary

This is a £4m call under the Global Challenges Research Fund (GCRF). This call has two stages, an Expression of Interest (EOI) followed by an invitation to submit a full application.  As the capabilities required to address antimicrobial target validation and drug discovery cover multiple disciplines, including basic bacteriology, computational biology, chemical biology etc., it is expected that successful collaborative proposals will draw on expertise across these disciplines. 

Background

The rapid rise in antimicrobial resistance across the globe poses a huge danger to human and animal health, threatening our ability to treat common infectious diseases and prevent infections following surgery and chemotherapy. Antibiotic resistant pathogens have been detected in every country but the problem is particularly pressing in Low and Middle Income Countries (LMIC), where infection rates are high, common diseases are often life-threatening and access to the already existing antibiotics can be limited. The current repertoire of antibiotics is increasingly ineffective and the threat is especially severe in the face of limited numbers of novel antibiotics. Urgent action is needed to accelerate new treatments for bacterial infection. However, antibacterial drug discovery is particularly complex due to various challenges, including keeping the drugs in the bacteria, the fast mutation rate of antibacterial targets leading to resistance and toxicity to the host. Promising antibacterial candidates are prone to failure at late stages of the drug discovery process because of low efficacy or safety, often owing to a lack of understanding and validation of the biological target. A multidisciplinary approach is needed to; enhance the understanding of antibacterial targets; develop new discovery platforms, reagents and tools; develop innovative new treatment paradigms; develop and investigate new disease challenge models; and revisit, repurpose or redesign the existing antibiotic toolkit.

Aim

To complement the wide range of research supported by the MRC in AMR, including through the Cross-Council AMR Initiative, and build on the UK’s excellent discovery bacteriology research, we now open the call for AMR Target Discovery and Validation (AMR TDV). This call will support between two and four multi-disciplinary networks/collaborations to develop innovative approaches to accelerate the antimicrobial pipeline, with a focus on LMICs. 

Research and scope

Taking into account the complex nature of target discovery and validation, and acknowledging that the expertise required for target validation do not always reside in a single laboratory or institution, we are looking to support consortia that can demonstrate the relevant skills and capabilities to manage a complex programme of work.

Successful proposals will include investigators from multiple research groups across relevant disciplines, including basic bacteriology, computational biology, chemical biology etc. Collaborations between groups based at different research organisations are particularly encouraged, including those based in LMICs. These awards are expected to support new networks and ways of working together. To enable productive and lasting collaborations, a small amount of funds may be directed towards network forming activities. 

Funding in the range of £1-2 million will be provided for a duration of up to three years. It is expected that between 2-4 proposals will be supported.

Successful target discovery and validation programmes of work will be informed by the needs of industry to generate suitable data packages for potential downstream antibacterial development. Collaboration with industrial partners is strongly encouraged, in accordance with MRC standard terms and conditions (see MICA guidelines), but should also consider how a partnership would fit with the principles of overseas development assistance and deliver short or long term health and wealth benefits to LMICs. 

Proposals will be assessed on; the strategy and novelty of the coordinating research priority(ies); the quality and skills of the research teams; and articulation of the potential outputs and downstream development plans (following on from this grant).

Consideration should be given to how the collaboration will use the requested funds and the governance structures in place to administer the funds amongst the participants. 

Proposals are expected to provide innovative solutions and collaborations to stimulate the development of new antibacterials that can be used in LMICs. The following research strategies will be considered, but not limited to;

  • Strategies to find new antibacterial targets e.g. discovery platforms, data mining, genetics.
  • Improved mechanistic understanding of new targets, the major systems targeted by existing antibiotics and mechanisms of resistance.
  • Approaches to revisit, refine or redesign existing or failed antibiotics
  • New approaches to screening e.g. new methods, assays, cell lines, clinical isolates.  
  • New animal challenge models, where this is a current barrier to validating antibiotics, to understand and investigate pharmacology, PK/PD and bioavailability etc.
  • New treatment approaches e.g. targeting new bacterial pathways, (c.f. virulence, persistence, resistance mechanisms, etc), targeting the host, antibody therapy, combination therapies.

The scope of this call does not include:

  • Full translational programmes developing or evaluating new antimicrobial interventions (see the MRC DPFS scheme)
  • Research that is not directly applicable to the health of LMICs.
  • Viral, fungal and parasitic resistance. The current focus of this call is on resistant bacteria of humans and animals but we acknowledge antimicrobial issues in other classes of pathogens are important.
  • Applications solely limited to screening chemical libraries.

Official Development Assistance

The research supported through this call will contribute to the UK’s commitment to Official Development Assistance (ODA) to Low and Middle Income Countries (LMIC).

Applications must demonstrate the research to be directly linked to near-term or long-term benefits to the health or prosperity of LMICs. This can include research on health issues of importance to both High Income Countries and LMICs where the direct potential impact on the research in LMIC is clearly explained.

Further guidance on ODA and demonstrating ODA compliance in applications for funding is available via the RCUK GCRF website, in particular ODA guidance. Applicants are encouraged to contact the MRC programme managers for further advice, using the email address DPFS&DCS@headoffice.mrc.ac.uk.

Eligibility

The Principal Investigator must be from a UK Research Organisation eligible to receive research council funding. Information about eligibility criteria can be found in our guidance for applicants. Researchers can be the Principal Investigator on only one application but may act as a Co-Investigator on any number of applications. LMIC-based researchers are welcome to apply as Co-Investigators. LMIC-based researchers may be affiliated with higher education institutions, non-profit research institutions or non-governmental organisations.

Call process

The call process will be in two stages:

  • Expression of Interest
  • Full Application

Expressions of Interest

Applicants will need to first submit an Expression of Interest using the Expression of Interest form. These will be assessed by MRC Board/Panel Members. Successful applicants will then be invited to submit a full application.

The purpose of the Expression of Interest is to ascertain the following:

  • Fit to AMR TDV remit
  • Fit with the principles of overseas development assistance and delivery of short or long term health and wealth to LMICs
  • Strength of scientific rationale
  • Strategy and novelty of the research approach
  • Quality and skills of the research teams
  • Potential outputs and downstream development plans (following on from the grant)

Assessment of Expressions of Interest will also take into account the MRC funding portfolio and current strategic priorities.

The MRC reserves the right to modify the process in the light of the actual number of Expressions of Interest received.

Expressions of Interest must use the Expression of Interest form and address the following:

  • Project title
  • Summary of the project

Please provide a summary of the project, including scientific rationale, fit to the AMR TDV call and management. Include in the summary how the research could be of benefit to the health of LMICs.

  • Details of Principal Investigator and Co-Investigators
  • Case for Support

Please include estimates of costs you anticipate will be required for the project.

Expressions of Interest should be submitted via your Research Organisation’s Administrative department to DPFS&DCS@headoffice.mrc.ac.uk

Full applications

If successful at EOI stage, applicants will submit full proposals which will be sent out for international peer review and assessed by an independent review panel convened by MRC. This panel will make the final funding decisions. Full proposals will be assessed on the standard criteria for an MRC research grant. 

Please note that the MRC reserves the right to amend the review process in the case of high demand.

Enquiries

Questions related to this call should be directed to DPFS&DCS@headoffice.mrc.ac.uk

Key dates

Expression of Interest:

Launch

3 October 2017

Deadline

3 November 2017

Panel Review

November 2017

Full Application Stage:

Opening

4 December 2017

Deadline

1 February 2018

Peer review

February – March 2018

Panel Review and Decisions

End of March 2018

Project start date

By 1 July 2018