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High-throughput sequencing hubs

This call is now closed for applications and is only available for reference purposes.

The MRC invites proposals for high-throughput sequencing hubs with associated technical and bioinformatics support.

£7.5 million funding is available to help develop and consolidate three to five regional hubs for three years initially (with a possibility of two further years support at a lower level). The hubs are expected to become self-sustaining thereafter.

Background to this investment

In response to demand from the scientific community the MRC Strategy Board has launched this initiative to strengthen UK-wide capability and expertise in high-throughput (HTP) sequencing. The investment will facilitate access to cutting-edge equipment and dedicated technical and bioinformatics expertise to allow biomedical and clinical researchers to fully realise the potential of these approaches.

The MRC sees a need for regional hubs with sufficient critical mass to allow:

  • the provision of dedicated expert support staff
  • an environment which enables close working with and expert advice to the scientists applying these techniques to a wide variety of areas
  • direct interaction with manufacturers in order to facilitate the iterative improvement of HTP sequencing technologies
  • efficient and effective use of the equipment

 

A hub functioning with critical mass will have at least three or four HTP sequencing machines and a minimum of two high-level technical or research assistant posts to oversee and run the equipment, together with at least one FTE bioinformatician.

The MRC is providing short-term pump-priming funding during a period of rapid expansion, improvement and establishment of this new technology. During this phase, consideration of the HTP sequencing services offered commercially will be necessary as this may be a significant factor in planning for the sustainability of the hubs at the end of the funding period. The aim of this investment is to catalyse self-sustaining expertise and capacity.

 

Expectations of the high-throughput sequencing hubs

Applications for hubs are expected to be from regional consortia. Each hub will be managed by a senior individual and a clear governance and management structure should be set out. The expectation is that each hub will:

  • provide scientific, technical and bioinformatics expertise and capacity in the application of high-throughput sequencing approaches in relation to the initial design of experiments, application of the techniques, sample preparation and the management, storage and analysis of the resulting data
  • have effective and active links with, and provide services to, a number of organisations in addition to the host institution (applications for hubs associated with only one intramural or extramural institution will not be considered in this call)
  • provide support/advice to the local/wider scientific and clinical communities. Interaction with NIHR, the devolved health administrations and NHS is strongly encouraged
  • all hubs will be expected to provide a service capacity for those outside the initial consortium submitting the application

 

Features of a successful application

The geographic location of the proposed hub will be a critical consideration during the assessment process and it is unlikely that more than one application from a single region will be successful. The detailed location of the Hub must facilitate direct interaction between researchers likely to utilise the resources and the hub staff and must enable easy access by other regional partners. The MRC intend to ensure, as far as possible, that there is an adequate geographical spread in the hubs.

 

Linking an MRC Hub with other existing/planned HTP sequencing systems or bioinformatics expertise is essential. Strengthening existing or planned HTP sequencing resources or expertise to enable the establishment of critical mass is a key ambition of this investment.

 

Hubs are primarily intended to fill the gap in HTP sequence service provision in the UK by providing support for small and medium sized projects. In general, there is an expectation that any large-scale projects (for example, de novo whole genome sequencing) should utilise large-scale specialised centres. Careful planning of workflows will therefore be critical to the success and full utilisation of the hub. Applications will therefore need to demonstrate, at the time of application, a commitment from a range of regional users and a clear understanding of the likely volume of work these users will generate. This commitment is expected at an individual researcher and senior level and should include the utilisation of this facility for current (active) MRC-funded projects or programmes. However, access to the expertise and facilities should not be restricted to those associated with the initial application or those who have active MRC funding.

 

A management and governance structure will be essential in order to ensure that the hub is providing open access and is utilised at full capacity. Applicants should consider how access to the facility will be prioritised and granted, for example, it is expected that priority would be given to projects that have already been subject to a rigorous peer-review process and that capacity provided by MRC would be used primarily for work relevant to MRC’s remit.

 

Funding arrangements

The MRC would prefer, where possible, to match funding provided by other sources. All applications will be expected to demonstrate existing or proposed funding (project co-funder) for equipment and/or staff posts (any funding not yet in place should be in the advanced stages of planning). Details should be given of project co-funders and their contributions, within ‘resource requested, Project co-funder’ section on the EAA. Other funding sources may include, for example, the host institution, the additional organisations involved in the application, NIHR, the devolved health administrations, charities and regional development agencies. MRC units/centres/institutes could allocate resource from their existing intramural quinquennial budgets. In all cases a strong commitment from the Vice Chancellor (or equivalent) of the host institution and other partner organisations will be required.

 

The expectation is that this MRC investment will enable the hubs to become self-sustaining facilities that eventually operate on a cost recovery model. Support for the activities and facilities provided by the hubs will be increasingly obtained via conventional grants. All hubs should expect to charge users consumable costs from the outset.

 

All hubs will be commissioned for three years initially, with a possibility of two further years support at a significantly reduced level for staff costs and consumables to underpin the transfer to a cost recovery model. Progress of all the hubs will be reviewed after two of the initial three years of funding, prior to the consideration of applications for renewal.

 

Financial support available

The MRC funding for a hub will support the initial resources required to enable the establishment or expansion of a HTP sequencing facility including, for example, staff costs, the purchase or lease of HTP sequencing machines, initial consumables and necessary computational resources for data storage and analysis. Applications can include contributions to salary for senior staff in leadership roles for the portion of their time dedicated to the hub. Consumables can be requested for methodology development and the development of the technology for new uses and approaches. Hubs will be able to stagger the requested investment across the three year funding period as required.

 

Funded hubs will receive a supplement for networking activities in order to share best-practice. Applicants need not include a request for funding for these Hub-networking activities at the point of application.

 

The MRC will fund on the basis of 80 per cent of the full Economic Cost (fEC) of the proposal. It is standard practice that where equipment costs exceed £50,000 in total then the amount above this figure will be paid in full (100 per cent fEC) and will automatically be considered as an exception (please refer to the MRC applicants’ handbook and using the EAA guidance).

 

Assessment criteria

All applications will be assessed on the basis of the case for support (business case) submitted and will be expected to provide information in the areas that will be considered by the assessment panel as listed below. It is critical that the consortium articulates a clear vision and strategic objectives for the hub. The case for support should explain the advantages of the proposed consortium and the benefits of this collaboration. Applicants must also justify the placement of the hub in terms of a research environment and accessibility for researchers.

 

In advance of the panel consideration the MRC programme manager will check two criteria:

  • Does the application demonstrate funding from other sources? Applications that do not demonstrate existing or proposed funding from other sources will not be considered by the Panel.
  • Is there more than one organisation involved in the application? Applications which do not substantially involve more than one intramural or extramural organisation will not be considered by the panel.

 

The specific criteria for the assessment panel to consider are:

Vision for the hub

  • Are the aims, strategic objectives and vision of the hub realistic, achievable and clearly articulated?
  • Would the proposed hub constitute a regional hub for excellence in HTP sequencing?
  • Will the hub provide a critical mass and high-quality expertise?

 

In summary, are the key components in place (or planned to be in place) to deliver the overall objectives of the hub?

 

Consortium arrangements

  • Does the application demonstrate effective links with, demand and commitment from a range of biomedical researchers (including those with MRC funding) and organisations?
  • Does the hub have sufficient senior leadership and is the nominated leader or hub manager appropriately skilled and experienced to ensure the aims and objectives of the Hub are delivered efficiently and effectively?
  • Is there an appropriate management and governance structure for the hub and its members?

 

Financial considerations

  • Is there sufficient financial commitment from the host and other organisations?
  • Have the applicants clearly set out the reasons for requesting the level of staffing and overall resources? Is this level adequate for the proposal?
  • Taking into account the expected outputs of the Hub and the level of resources requested, does the application promise good value for money?
  • Will this hub become self-sustaining within a five-year timeframe?

 

Additional considerations

  • Is there adequate geographical spread in the proposals selected?
  • Are the applicants committed to providing advice and support to the local/wider scientific and clinical communities?

Please note that geographical spread will only be considered at the final stage of the assessment process once all other factors have been taken into account. The most important factors will be the vision, the demonstration of potential demand and the financial considerations.

  

Case for support (business case)

In addition to completing the specific fields requested in the EAA, you will need to submit a case for support (business case) which must be attached as a PDF to the EAA application. The case for support may be up to ten A4 pages in length, including references, using Verdana 10pt typeface with margins of 2cms on the left hand side and 1.5cms on other edges.

Your case for support (business case) should address each of the points raised within the Assessment Criteria.

There should be no addition of annexes without prior agreement from MRC Office Scientific Contact (Programme Manager), Dr Joanna Jenkinson.

 

Terms and conditions

  • All Hubs are subject to the acceptance of the MRC’s normal grant conditions.
  • In addition, and with respect to the RG21 Commercial Exploitation, where the Hub is providing a service, ownership of intellectual property (IP) and responsibility for its exploitation rests with the user’s research organisation. For collaborative research hubs should negotiate, in advance, a clear arrangement regarding ownership of IP and the responsibility for exploitation.

 

Data sharing and preservation strategy

All MRC grant holders are required to have a data sharing policy in place. You must include a data sharing and preservation strategy statement in line with MRC policy, and data access principles. Hubs will need a specific data sharing, retention and short to medium-term preservation policy in relation to the raw data generated and the compiled data transferred to users. It is not expected that every read/run will be preserved for the same period of time or for a long period. In terms of data sharing, the sequencing and bioinformatics methodologies used by the Hub should be freely available to users as part of the study metadata.

 

The hubs will be expected to have the expertise to support or facilitate the development of user data sharing policies where necessary. Users will be the primary customers of the generated data, but Hubs will need the capability to advise on good practice in relation to data handling, storage and preservation and be pro-active in the use of standards for handling raw, analysed and metadata.

 

Your statement should include plans for facilitating data deposition where an appropriate preservation infrastructure is available (for example, a community or institutional database/archive). In this context, there should be a clear policy in relation to the format of the data output from the hub.

 

If the data relates to human participants and is personally-identifiable, you should ensure the user has the necessary statutory, regulatory and ethical approvals in place in advance of the hub providing a service to the User. It is essential that the hub maintains very high standards of confidentiality when experiments involve personally-identifiable samples. In this respect a clear policy and robust systems to deliver the confidentiality and security of data, will need to be in place in advance of the operation of the hub.

 

You may wish to consult MRC guidance on dataset discovery, governing access and use, data sharing agreements, data from research involving people, research proposals and funding access.

  

Assessment panel

Proposals will be assessed by a specially convened expert Panel. The decisions of this Panel are not open to appeal and MRC reserves the right to change the process outlined below if necessary. The Panel Chair will be John Jeans, MRC Chief Operating Officer and Deputy Chief Executive. The Panel will include representation from MRC’s Strategy Board, MRC’s Molecular and Cellular Medicine Board and include expertise in:

  • HTP sequencing techniques
  • Bioinformatics
  • Running service facilities

 

The panel membership will be available once confirmed. There will be no written peer-review process and feedback to applicants is likely to be limited. The panel will meet towards the end of March and applicants will be notified of the outcome in early April.

 

Frequently Asked Questions

Q: I want to be able to use a hub in the future but my institution is not part of a consortium bid, will this be possible?

A: Hubs are expected to be open to all requests for use of their facilities and expertise, in accordance with transparent criteria for prioritising access. Applicants wishing to utilise the hubs would be expected to include the costs of utilising this resource in grant applications or cover costs from existing funding. For grant applications requesting funding for use of the hub, the hub manager should be aware of this request in advance of submission and confirm that access will be available if the proposal is successful.

 

Q: What do I do if I want to use my local hub but they are at full capacity?

A: If appropriate, applications to place further equipment within an existing hub will be permissible if further capacity or technology development is required and clearly justified. A collaboration grant involving the Hub identifying the additional users of the technology could potentially be envisaged.

 

Q: I want to apply for a HTP sequencing system via a collaborative grant but outside a specialised hub, is this possible?

A: This investment does not preclude the request for individual HTP sequencing machines outside the hubs via collaboration grants where appropriate. However, hubs are expected to add value in the areas of technical expertise and bioinformatics knowledge, therefore, clear justification for placing an HTP sequencing system elsewhere and evidence of access to sufficient technical and bioinformatics expertise will be required. This justification would need to demonstrate that the groups could fully utilise the capacity offered by the system and the equipment should be run alongside other local sequencing machines wherever possible.

 

Q: What is the background to this investment?

A: In June 2008 MRC convened a group of experts in order to review the provision and application of HTP sequencing, as part of MRC’s strategy in genetics and genomics. The group reviewed developments in high-throughput sequencing, its potential impact in biomedical research and the current availability of the technology in the UK. The group recommended to MRC’s Strategy Board funding a few medium sized centres, with associated technical and bioinformatics expertise to support small and medium sized projects.

 

Contact

Any queries should be discussed with Dr Joanna Jenkinson at MRC Head Office.

Dr Joanna Jenkinson
Telephone: 020 7670 5020
Email: joanna.jenkinson@headoffice.mrc.ac.uk

 

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