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.
|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|
Any UK research establishment including:
Applicants should be UK-based researchers who can demonstrate that they:
Applications involving less experienced researchers should be made in collaboration with a more senior colleague
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.
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
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
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
The following Panel will consider applications submitted to this call.
|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|
A total budget of £30k is available for this Strategic Award call. A maximum of one award, of up to six months in duration, will be made. The financial support requested should be dictated by the scientific need of the project.
- NC3Rs Applicant and Grant Holder Handbook
- Call specific- Additional guidance for writing the case for support
- MRC Guidance for Applicants and Award Holders
- Strategic Award panel scoring criteria - call specific