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Human Cell Atlas

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​​​​Objective

The MRC is seeking to invest in groups across the UK to support the UK’s partnership in the international Human Cell Atlas (HCA) programme. The HCA aims to create a comprehensive reference map of all human cells as the basis for understanding human health and diagnosing, monitoring and treating disease.

Through this initiative we aim to bring together cell biology, precision molecular analytics, multi-scale imaging and cutting-edge bioinformatics to contribute to the international efforts to help define all the human cell types in terms of their distinctive patterns of gene expression, physiological states, developmental trajectories and location. Participation in the HCA will ensure the highest international standards of data analysis, management and co-ordination and will provide significant pull for the development of new subcellular imaging tools and modalities.

We have secured up to £5.5m to support these ambitions. Additional partnership funding from the British Heart Foundation is also available, subject to competitive bids targeted at tissues of the cardiovascular system. 

Funding is available to support well-established research groups to undertake single cell gene expression and image analyses in matched developmental (embryonic and foetal) and adult tissues. Researchers who have a demonstrable track record in single cell analytics, imaging or elucidating foetal and adult tissue function are invited to apply for funding.

We expect to make 10-12 awards towards the end of November 2018. The awards will be a little over two years in duration and approximately £450k in value. The initiative aims to deploy funds rapidly to ensure early engagement of UK researchers with the international efforts. Awards must start by mid-December 2018.

Applicants must already have research ethics permission for human tissue analysis in place and have ready access to tissue samples from healthy adults. Where possible these will be analysed alongside the corresponding developmentally-staged tissues from the UK Human Developmental Biology Resource (HDBR). Funds will be available for single-cell RNAseq/ATACseq analysis and cell imaging across different scales of resolution.

Awarded groups will be required to become HCA project partners and adhere to HCA standards, submitting their data to the HCA Data Co-ordination Platform (DCP) and helping to co-ordinate tissue and disease foci within the HCA consortium.

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Background to this investment

Human Cell Atlas

The Human Cell Atlas (HCA) is an international partnership that has been established to create a comprehensive reference map of all human cells as a basis for understanding human health, and diagnosing, monitoring and treating disease.

Despite progress in the fields of cell biology and histopathology over many decades, only with recent technological innovations has it become possible to contemplate systematically identifying, characterising and functionally defining all of the cell types in the human body. With this aim, and analogous to the Human Genome Project of the 1990s, the HCA international collaboration will make data freely available to researchers around the world, not only increasing knowledge but also providing new insights into human disease and driving technology development. One of the flagship activities of the HCA is the development of a Data Coordination Platform (DCP), which is jointly led by the EMBL-EBI (UK), the Broad Institute (US) and University of California, Santa Cruz (US). The DCP has been established to ensure that all HCA data is validated, associated with high quality metadata and made available to the wider scientific community. As part of this the EMBL-EBI is leading activities to ingest, process and make available single cell data (including RNASeq/ATACseq and imaging) generated through the HCA activities.

The management and interrogation of these rich datasets requires specialist skills in bioinformatics and computational biology, and through this initiative we will work with the EMBL-EBI to provide new training courses in the analysis of RNAseq/ATACseq data to enhance UK skills in the area.

Human Developmental Biology Resource

The Human Development Biology Resource (HDBR) is a unique UK resource, which we have jointly supported with the Wellcome Trust since 2002. One of only a few worldwide, the HDBR provides embryonic and foetal material for research. Material is available at various stages of development, from 4-22 weeks of gestation, in fresh, frozen or fixed states.

We will provide additional funding to the HDBR to allow it to collaborate with the recipients of HCA awards and provide researchers with developmentally-staged tissue for comparison with adult tissue.

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Expectations of the awards

Tissue focus

Funds will be available on a competitive basis to researchers with a demonstrable track record in single cell analytics, imaging (level of resolution can range from single cell to whole organ) or elucidating foetal or adult tissue function. Researchers must already have research ethics permission for human tissue analysis in place and should have ready access to tissue samples from healthy adults. The number of samples will depend on the accessibility and complexity of the tissue, but a minimum of 3 age and sex-matched samples should be available. Where possible these should be analysed alongside matched developmental (embryonic or foetal) tissues from the HDBR. Please note that separate ethical approval is not required for research teams in the UK receiving HDBR material, as the Research Tissue Bank ethics approval of the HDBR covers research by end-users. Established groups in the areas of experimental medicine, stratified medicine, imaging and tissue banking will be well equipped to participate. Within the application there must be a clear statement confirming that all the necessary ethical approvals are in place and that adult tissues are available in accordance with the project and spend plan.

Funding will made available under standard FEC principles using TRAC methodology but should be primarily focussed on consumables, staff time and any essential novel imaging equipment to deliver RNAseq/ATACseq analysis and associated imaging to capture the spatial mapping of the cells.

To maximise the opportunity for the UK community to engage with, and contribute to, the international ambitions of the HCA programme, we are seeking to support the analysis of a broad array of different human tissues, expanding on the efforts of the Wellcome Trust through their recent HCA initiative. The choice of tissues will need a clear scientific rationale and may be focussed on those within a single organ system where compelling arguments are made. In this regard we are keen to encourage applications focussed on the heart and broader cardiovascular system, which could secure co-funding from the British Heart Foundation.

Data management

Data generated by projects funded through this initiative are expected to be compatible with the standards and data storage technology developed by the HCA and implemented by the HCA Data Coordination Platform (DCP). Data produced by the awarded groups will need to be deposited within the DCP and made openly available through the DCP to the world-wide research community prior to publication. This will enable the scientific research community to interact freely with the data via existing portals and integrate different HCA datasets via common use of data standards and storage solutions. We recognise that researcher engagement and subsequent data submission to the HCA DCP requires support and coordination. We will work with EMBL-EBI to provide broad user support and data submission and release activities. Successful applicants should liaise with the EMBL-EBI at the earliest opportunity by emailing devatlas-dcc@ebi.ac.uk.

In addition a meeting between awardees, the EMBL-EBI team and HDBR and other HCA leaders will be scheduled early in the implementation phase to facilitate data generation and co-ordination.

Spend

Awards will start no later than mid-December 2018 and applicants must be able to initiate their work rapidly to meet our expectation of £1.5m spend (of the £5.5m) by the end of March 2019. This means that each award is expected to spend 30% of its funds before 31 March 2019.

Each application must include an attachment that presents a spend plan and quarterly spend profile for the entire award and which meets the rapid spend requirements above.

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Financial support available

Funding will support awards of around £450k each (MRC contribution) according to standard FEC principles using TRAC methodology; funds should be directed towards single cell analysis (primarily RNAseq or ATACseq) and imaging, and associated staff time.

Funds can support:

  • adult tissue collection, retrieval and processing
  • consumables and any access costs to analytical equipment
  • technician/researcher time 
  • project-specific travel to support collaborative activities
  • limited investigator time (no more than 2 hours per week each)
  • costs of attending HCA meetings.

Limitations to financial support:

  • Capital funding for microscopes and flow cytometers is not available through this call – although requests for equipment to support non-invasive tissue imaging will be considered where an exceptional case is made.
  • Costs related to obtaining ethics approval, publication costs or travel to non-HCA related conferences are not eligible. 

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Eligibility

This call follows standard MRC and UKRI eligibility criteria and is open to all UK-based researchers who can show they will direct the proposed research and be actively engaged in carrying it out. Eligible institutions include UK higher education institutions and all Independent Research Organisations (IROs) listed on the UKRI web page.

Applications involving collaboration with industry should adhere to the MRC Industry Collaboration Agreement guidance. The lead applicant must be the academic partner, and we will meet the academic costs of the project only. If you are considering involving an industry project partner, please contact us during the application process.

Applicants are reminded to list all relevant live grants in their application. Where current funding includes similar single cell transciptome analysis (e.g. through recent Wellcome Trust and Chan Zuckerberg initiatives), applicants must clearly articulate how an MRC investment would be distinctive and provide strategic added value to existing funding.

We strongly advise applicants to discuss any matters of uncertainty with us before submission by contacting HCA@mrc.ukri.org.

For this call only: Public Sector Research Establishments (PSREs) with 10 or more researchers with PhDs (or equivalent) are eligible to apply. If PSREs wishing to apply have not previously applied for UKRI funding and are not currently designated IRO status they will be required to complete an eligibility form to ensure they have the required research capacity, systems and controls in place to manage the research and grant funding. PSRE applicants should contact HCA@mrc.ukri.org at the earliest opportunity to discuss their interests in applying.  

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How to apply

Applications will be managed through a single-stage review process and applicants should follow the steps below. Applicants should also review the general guidance for applicants:

Step 1: Applicants wishing to access foetal/embryo tissue must contact the HDBR on hdbr@ncl.ac.uk or hdbr@ucl.ac.uk at the earliest opportunity to discuss tissue availability, register their project and arrange for an MTA. The HDBR will advise on developmental staging, tissue processing and preparation, tissue availability and timeframes. The availability of fresh tissue is limited, particularly at certain developmental stages (under six weeks and over 13 weeks of gestational age), and applicants will need to consider the merits and logistics of using fresh or frozen tissues. Applicants are reminded that 30% of their budget request should be spent before the end of the current financial year ending 31 March 2019. Applications will not be accepted where the desired tissues are unavailable within a suitable timeframe to allow you to meet these spend conditions.

Written confirmation from HDBR to verify the availability of tissues and associated timeframes should be included as an attachment to your application. Failure to do so will result in rejection of the application. HDBR will cover shipping costs.

Step 2: To ensure that the output data (e.g. RNASeq/ATACseq and imaging) includes the appropriate metadata and is compatible with the standards and data storage needs of the HCA partnership, applicants should contact EMBL-EBI colleagues at the earliest opportunity by emailing devatlas-dcc@ebi.ac.uk.  

Within the application there must be a clear statement confirming that applicants have fully engaged with the EMBL-EBI and their plans conform to the needs of HCA regarding experimental design and analyses, data acquisition and release.

Step 3: Complete the application process using the standard MRC online Je-S form, selecting Document type: Standard Proposal, Scheme: Research Grant and Call name: Human Cell Atlas.

The Case for Support should be no more than 8 pages.

The following additional attachments are required: 

  • Analysis involving developmental tissue from the HDBR, will require written confirmation from the HDBR that the required tissue (fresh and/or frozen) will be available and the indicative timeframe of provision. This will need to align with your spend plan below and should be uploaded as a ‘letter of support’ document on Je-S.
  • Spend plan and quarterly spend profile that meets the needs for 30% spend in FY2018/19. Please complete the spend profile template and upload this and any further documentation as the ‘supporting data’ document type.
  • Optional letters of support from key collaborators or partners (under document type Supporting Data – no more than 2 pages per letter).
  • A CV for the Principal Investigator, any Co-Investigators and named individual research staff (no more than 2 pages).
  • A Publications list for the Principal Investigator, any Co-Investigators and named individual research staff (no more than 1 page each).
  • Justification of resources (maximum 2 pages)
  • Data management plan (maximum 3 pages)
  • Pathways to impact document (maximum 2 pages)
  • MICA and Heads of Terms forms should be appended if the study involves collaboration with industry. Please contact HCA@mrc.ukri.org when planning to include industry partnerships.

A reproducibility and statistical design annex is not required. All attachments should use Arial 11 point. Please refer to the Applicants’ Handbook for further information on document requirements.

You must submit your application to us by 4pm (16:00 GMT) on 6 November 2018.

For queries regarding preparation and submission of your application please contact the Je-S helpdesk:

Je-S Helpdesk

 Monday to Thursday 8.30am to 5pm and Fridays 8.30am to 4.30pm (excluding bank holidays and other holidays)

Telephone: +44 (0) 1793 44 4164
Email: JeSHelp@rcuk.ac.uk
Web: https://je-s.rcuk.ac.uk

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Assessment criteria

Applications will be assessed, and funding decisions reached, towards the end of November 2018 by a panel of national and international experts that is convened specifically for this call. Additional referee comments will not be sought. Funding decisions by the panel will be final and applicants will not have the opportunity to respond to any issues raised.

Applications will be evaluated against the following criteria:

  • Does the proposal meet the aims and expectations of the call and offer an important contribution to the UK’s partnership in the HCA?
  • Does the team have the necessary expertise and experience to carry out the proposed study?
  • Does the project have ready access to the necessary analytical equipment (i.e. single cell transcriptome sequencing and cellular imaging), other than where there is an exceptional case for purchasing tissue imaging equipment?
  • Is it clear that the applicants have timely access to adult tissues, and any matched foetal/embryo tissue from the HDBR?
  • Is the study as a whole well-designed, with robust experimental design and the necessary link up with the HCA DCP through the EMBL-EBI?
  • Have the applicants confirmed that all the necessary ethical approvals for tissue collection and use are in place?
  • Will the activities be appropriately managed?
  • Is the project feasible and does it offer value for money?
  • Does the application include an attachment that provides a clear and robust project and spend plan that meets the rapid spend requirements of this call?

Applicants should check their completed application forms against the assessment criteria above prior to submission to make sure that they have addressed all points. There will be no opportunity to amend applications after submission and applications will be rejected if they do not comply with the requirements.

Through this initiative we aim to support the HCA goal of mapping all cells in the human body. Whilst quality of the application is paramount, the final investment will also seek to maximally deliver a broad array of tissue and a good geographical distribution of awards.

Please note that on request, only high-level feedback will be provided to applicants following the panel’s decisions.

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Key dates

Call opens

24 September 2018

Call closes

6 November 2018

Panel meeting

23 November 2018

Latest start date for awards

Mid-December 2018

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Contact

If you have any queries regarding remit, eligibility and acceptable costs please contact HCA@mrc.ukri.org

For assistance with the Je-S application system please contact the Je-S helpdesk:

Telephone: +44 (0) 1793 44 4164
Email: JeSHelp@rcuk.ac.uk
Web: https://je-s.rcuk.ac.uk

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