Small molecule high throughput screen using AstraZeneca facilities (Grant)

About this opportunity

Word limit: 550 In plain English, provide a summary we can use to identify the most suitable experts to assess your application. We usually make this summary publicly available on external-facing websites, therefore do not include any confidential or sensitive information. Make it suitable for a variety of readers, for example: opinion-formers policymakers the public the wider research community Guidance for writing a summary Clearly describe your proposed work in terms of: context the challenge the project addresses aims and objectives potential applications and benefits Core team List the key members of your team and assign them roles from the following: project lead (PL) project co-lead (UK) (PcL) specialist grant manager professional enabling staff research and innovation associate technician researcher co-lead (RcL) Only list one individual as project lead. If you include more than one project lead your application will fail at the checking stage. UKRI has introduced a new addition to the ‘Specialist’ role type. Public contributors such as people with lived experience can now be added to an application. Find out more about UKRI’s core team roles in funding applications . Application questions Vision Word limit: 1,100 What are you hoping to achieve with your proposed work? What the assessors are looking for in your response Explain how your proposed work: is of excellent quality and importance within or beyond the field has the potential to advance current understanding, or generate new knowledge, thinking or discovery within or beyond the field is timely given current trends, context, and needs Within the Vision section we also expect you to: describe the unmet need for new therapeutic approaches to the disease of interest describe how the target is involved in the pathology or aetiology of the disease of interest describe how manipulation of the target could produce disease modifying effects Complete the table available in the Funding Service and paste as a figure into the Vision section including the following: target name target type, for example soluble cytokine, cell surface protein mechanism of action, for example agonist, antagonist proposed therapeutic use, for example disease, subpopulation route of administration and dosing frequency, for example IV or sub-cutaneous with daily or weekly dosing frequency, which are acute or chronic References may be included within this section. You may demonstrate elements of your responses in visual form if relevant. Further details are provided in the Funding Service. Approach Word limit: 2,500 How are you going to deliver your proposed work? What the assessors are looking for in your response Explain how you have designed your approach so that it: is effective and appropriate to achieve your objectives is feasible, and comprehensively identifies any risks to delivery and how they will be managed uses a clearly written and transparent methodology (if applicable) summarises the previous work and describes how this will be built upon and progressed (if applicable) will maximise translation of outputs into outcomes and impacts describes how your, and if applicable your team’s, research environment (in terms of the place and relevance to the project) will contribute to the success of the work Within the Approach section we also expect you to: demonstrate access to the appropriate services, facilities, infrastructure, or equipment to deliver the elements of the project to be conducted outside the AstraZeneca facilities provide a project plan for the assay cascade beyond the initial HTS run in the form of an embedded schematic describe your approach to ethical and regulatory approvals and their status. Consider the MRC guidance on ethics and approvals explain and justify any use of human tissues or biological samples, including the type of material to be used, quantity required, and its source You should consider the following (guides not requirements). Safety: cells, including GMO and hazard group reduction or removal of any high-risk reagents Cost: commercial reagents and microtitre plates, and any bulk discount options Screening cascade: identify the most appropriate assay format, considering practicality and suitability for identifying hits orthogonal or artefact assays post-HTS in place that are suitable for triaging primary output Reagents: feasibility to produce or purchase enough reagents for HTS stability of reagents in storage and on bench (HTS environment and over run timescale) relevant tool compound if available to validate and to use as control compound Assay process: 384 or 1,536 well plate compatible minimise number of assay steps or dispenses preferable to use assay ready plates rather than requirement for plate-to-plate transfer Quality control criteria: Z’ > 0.5 signal to background > 3 %CV of a max control plate reproducibility of tool compound (pXC50 +/- 0.5log) Screen strategy: number of compounds to screen, based on cost and assay throughput You do not need data related to all elements of the above, as work can be undertaken as part of the screen set-up work at AstraZeneca to establish that all parameters are appropriate prior to the HTS being run. However, the viability of the approach may be impacted if there is insufficient data to demonstrate that the assay would be viable. If you are proposing a phenotypic assay, then additional considerations need to be discussed in your application and incorporated into your proposed orthogonal screening components. These will include: ensuring that sufficient amounts of the proposed cell line can be generated for the screen ensuring that the number of steps and readouts remain amendable to utilisation in a high throughput capacity selecting assay features and primary readouts that can be connected to clinical responses or outcomes avoiding multiple primary readouts and instead identifying the key readouts and adding additional readouts into the confirmatory phase of the screening cascade clearly explaining how the number and diversity of mechanisms that may be active in the primary screen will be handled during the cascade pre-identifying potential known mechanisms, to be included or excluded, so that confirmation assays can be readily executed in order to eliminate key known mechanisms or prioritise novel mechanisms explaining how you will incorporate assays that eliminate technical false positives and undesirable mechanisms explaining any future deconvolution steps to be undertaken post award and framing the strategy for onward new medicine development steps References may be included within this section. You may demonstrate elements of your responses in visual form if relevant. Further details are provided in the Funding Service. Resources and cost justification Word limit: 1,000 What will you need to deliver your proposed work and how much will it cost? What the assessors are looking for in your response Justify the application’s more costly resources that relate to work to be conducted outside of AstraZeneca. Costs incurred at AstraZeneca (do not need to be justified but must be included in your request to MRC) should be: £150,000, 100% exception costs relating to staff and consumables at AstraZeneca (justification is not required for fixed costs) £20,000, 100% exception costs related to AstraZeneca optimising the assay, looking at alternate readouts and running a feasibility panel (justification is not required for fixed costs) These costs should be entered altogether, that is £170,000, under the ‘Exceptions – Other’ heading. Costs incurred at the research organisation should be: up to £100,000 full economic cost (£80,000 MRC contribution) to costs incurred at the research organisation for follow up assays (this figure to also include cost of sending a researcher to AstraZeneca for up to three months) Justify the application’s more costly resources, in particular: project staff significant travel for field work or collaboration (but not regular travel between collaborating organisations or to conferences) any equipment that will cost more than £25,000 any consumables beyond typical requirements, or that are required in exceptional quantities all facilities and infrastructure costs all resources that have been costed as ‘Exceptions’ You can request costs associated with reasonable adjustments where they increase as a direct result of working on the project. For further information see Disability and accessibility support for UKRI applicants and grant holders . Where a funding limit is imposed on the opportunity, requested costs for reasonable adjustments may exceed the maximum funding amount. Assessors are not looking for detailed costs or a line-by-line breakdown of all project resources. Overall, they want you to demonstrate how the resources you anticipate needing for your proposed work: are comprehensive, appropriate, and justified represent the optimal use of resources to achieve the intended outcomes maximise potential outcomes and impacts Applicant and team capability to deliver Word limit: 2,000 Why are you the right individual or team to successfully deliver the proposed work? What the assessors are looking for in your response Evidence of how you, and if relevant your team, have: the relevant experience ( appropriate to career stage ) to deliver the proposed work the right balance of skills and expertise to cover the proposed work the appropriate leadership and management skills to deliver the work and your approach to develop others contributed to developing a positive research environment and wider community You may demonstrate elements of your responses in visual form if relevant. Further details are provided in the Funding Service. The word limit for this section is 2,000 words: 1,500 words to be used for Résumé for Research and Innovation (R4RI) modules (including references) and, if necessary, a further 500 words for Additions. Use the R4RI format to showcase the range of relevant