Development of an Adverse Outcome Pathway (AOP) for Cardiotoxicity

This call is closed

Focus

An adverse outcome pathway (AOP) links a molecular initiating event (MIE) caused by a chemical or drug interaction with a biological system at a molecular or cellular level, with undesired endpoint(s) (‘adverse outcomes', AO) in an organism or population, through a scientifically proven chain of causally related key events (KEs). Increased mechanistic understanding of events in a pathway can facilitate the development of in vitro or in silico approaches to predict the likelihood of a subsequent AO, in place of animal tests. In recent years, there has been a growing interest in the application of mechanistic or pathways-based approaches for human and environmental safety assessment of chemicals and pharmaceuticals, since identification of hazardous compounds earlier in drug or product development could reduce the number of compounds that go on to further compulsory tests in animals. The NC3Rs has a programme of work to increase awareness of AOPs and encourage their use as part of a new approach to human and environmental safety assessment.

Cardiotoxicity was identified as an area of potential interest for AOP development by a network of collaborators convened by the NC3Rs and the European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) in 2015. These cardiovascular research experts from industry, academia and clinical sectors proposed investigation of two cardiotoxicities of concern: reduced cardiac contractility (inotropy) and structural cardiotoxicity.  Initial mapping of known information from literature created skeleton AOPs for further development. In June 2016, one of these cardiovascular topics was accepted as a project onto the OECD work plan, entitled ‘L-type Ca2+ channel block leading to heart failure’.

We are seeking applicants to:

  • Develop the AOP on ‘L-type Ca2+ channel block leading to heart failure’.
  • Conduct detailed literature searches to define the key events and build the weight-of-evidence for key event relationships along the pathway.
  • Define the methods that can be used to observe or measure the key events along the pathway.
  • Provide evidence for the AOP using reference substance information from literature.
  • Provide outputs in the form of a completed OECD application template and a comprehensive review manuscript describing the AOP pathway.

Key datesWho can apply | How to apply |  Assessment procedure Assessment Panel | Resources and awards 


Key dates

29 March 2017  Application form live on Je-S
26 April 2017, 4pm Deadline for full applications via Je-S
June 2017 Panel meeting for full applications
June 2017 Applicants notified of outcome
1 July 2017 Expected project start date
1 September 2017 Latest date for commencing projects
13 September 2017 Grant Holder introductory meeting

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Who can apply

Establishment eligibility

Any UK research establishment including:

  • Higher Education Institutions (HEIs)
  • Independent Research Organisations (IROs)
  • Research Council (RC) Institutes
  • Industry (Small to medium enterprise) EU definition of SME

Individual eligibility

Applicants should be UK-based researchers who can demonstrate that they:

  • Will direct the proposed research
  • Will be actively engaged in accomplishing the project’s aims
  • Have a PhD

Applications involving less experienced researchers should be made in collaboration with a more senior colleague

Overseas researchers

Overseas researchers cannot be primary investigators but can be included as collaborators. Overseas co-applicant status can be obtained in exceptional circumstances and at the discretion of the NC3Rs; approval should be sought before applying.

Resubmissions

The NC3Rs does not allow resubmission of previously unsuccessful proposals, unless explicitly invited by the Panel. Proposals previously declined by the NC3Rs will not be considered by another Research Council or funder within 12 months (from the date of submission to the original Research Council) unless substantially revised. More information can be found in the NC3Rs Applicant and Grant Holder Handbook.

Please note: The same or similar application cannot be considered by any other Research Council, the Health Departments or any other research funder at the same time

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How to apply 

This call is now closed - Applicants are advised to read and refer to the NC3Rs Applicant and Grant Holder Handbook, which contains more detailed information on submitting an application

Applications received after 4pm on the deadline date will not be considered, without exception.

Submitting a full application

We use the Research Councils' joint electronic submission system (Je-S) and applications are processed by the RCUK Shared Business Services.

Please note - For this call, the page limit for the case for support attachment is four sides of A4. Applicants are advised to read the call specific additional guidance provided for writing the case for support before completing their application

If you experience difficulties using Je-S or have questions regarding its use, contact the Je-S helpdesk.

Email: JeSHelp@rcuk.ac.uk     Phone: +44 (0) 1793 44 4164

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Assessment Procedure

Applications are evaluated by the NC3Rs Strategic Award Panel.

The following criteria are taken into consideration when making funding decisions:

  • Relevance to the strategic call
  • Knowledge of AOP process
  • Applicant track record
  • Demonstration of appreciation for pathways-based approaches to impact the 3Rs
  • Likelihood of successful project delivery
  • Promotion of proposed research to the scientific community
  • Justification for resources

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 Assessment Panel 

The following Panel considered applications submitted to this call.

Member name  Institution
Professor Blanca Rodriguez (Chair) University of Oxford
Dr Maria Beaumont  GlaxoSmithKline
Dr Mark Holbrook VAST Pharma Solutions
Dr Brigitte Landesmann European Commission
Dr Amy Pointon AstraZeneca

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Resources and awards

A total budget of £30k was available for this Strategic Award call.

One award of six months duration was made in May 2017.

Dr Luigi Margiotta-Casaluci

(Brunel University)

Development of an AOP for cardiotoxicity mediated by the blockade of L-type calcium channel

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