A New $55M PROGRAM
Delta Tissue
INTEGRATED PLATFORMS FOR PREDICTING CHANGES IN TISSUE STATE
A NEW $55M PROGRAM
Delta Tissue
INTEGRATED PLATFORMS FOR PREDICTING CHANGES IN TISSUE STATE
A NEW $55M PROGRAM
Delta Tissue
INTEGRATED PLATFORMS FOR PREDICTING CHANGES IN TISSUE STATE

The pandemic has revealed how much work there is to do in advancing and protecting human health. More than 2.5M people died after infection with SARS-CoV-2 and millions more suffer from its long-term effects. The costs to individuals, families and society are immeasurable.

But the pandemic has also revealed what a difference a scientific breakthrough can make. The scientific and pharmaceutical communities developed revolutionary mRNA vaccines on timescales 10 times faster than was previously thought possible. This advance is saving millions of lives and preventing millions of lost person-years of disability and distress.

We’ve witnessed a remarkable feat of science, collaboration, and global response that shows what is possible. It’s a proud moment for science, but there’s so much more to do.

Beyond the millions lost to COVID-19, 2020 and the years before it were tragically normal. In recent years, we have lost:

  • 10M people/year to all forms of cancer
1.8M people/year to lung cancer, 685K people/year to breast cancer
  • 1.4M people/year to tuberculosis (TB)
  • 435K people/year to malaria

Without new advances, 2021 and the years that follow will look much the same.

These diseases have something in common. They are all ultimately caused by changes in the molecules and cells that define how a tissue functions and interacts with the other tissues in our bodies. If we could understand the physiological state of a tissue, we could explain the status of a disease in each person and better predict how that disease would progress.

In the case of TB, we know that immune system responses in more than 90% of the 1.7 billion people exposed to Mycobacterium tuberculosis (or “Mtb”), the active agent of tuberculosis, will successfully manage or even clear the disease. But, the remaining 10% of the world’s infected population propagate a disease that kills more people annually than any other. The antibiotics we have to fight TB require at least 6 months of regular treatment. Many people don’t complete the therapy and this has led to the development of antibiotic-resistant TB, which is cited by the WHO as one of the most significant threats to global health. It is a rapidly growing epidemic in India, China, the Russian Federation and much of Asia. We cannot tell who will clear TB on their own and who needs help, so we over-prescribe antibiotics, increase the risk of antibiotic resistance, and make the TB epidemic even worse.

In the case of cancer, we know that ~30% of the population in industrialized countries will be diagnosed with cancer in their lifetimes and 10% of all deaths will be due to the disease. Diagnosing many forms of cancer earlier in disease progression has improved survival rates, and in some cases, we can intervene successfully. But for a frustratingly large number of patients, our therapies extend life by mere months, instead of providing cures.

We must do better.

We know that infectious and noncommunicable diseases act at the levels of molecules, cells and tissues, so at least part of the solution resides in measuring and understanding their states. Whereas we used to think of cell transitions as one-way and irreversible, we now see that in many cases cells transit between states, sometimes reversing themselves as they respond to changing conditions. These cell and tissue dynamics are new territory that we must detect, quantify, and ultimately model. Measuring the properties of cells and tissues requires technologies that are expensive to buy and run, and require expert, well-trained staff who are in short supply — tools should be much more widely accessible to academic centers, start-ups, SMEs, the whole biopharma industry, and ultimately to clinicians and patients for diagnostic use.

Program goals.

We need a new platform – a ‘tissue time machine’ – that can profile tissue states and predict transitions between states (‘Delta Tissue’ or ‘ΔT’). The platform would provide quantitative, multi-scale, multi-modal information sufficient to build integrated prediction models of key cell and tissue states and transitions. If we are successful, we’ll be able to intervene in diseases earlier and with approaches that are targeted to the individual. We’ll also have an improved understanding of the mechanisms that drive disease, which, in turn, will provide more opportunities for intervention. If we succeed, we’ll begin to eradicate the stubbornly challenging diseases that cause so much suffering around the world.

Such a platform is now possible if we combine the latest cell and tissue profiling technologies with recent advances in machine learning and other computational methods. With this foundation, we can now imagine the tissue time machine, which assembles a rational set of profiling modalities, integrates their outputs and builds predictive models of tissue states and transitions.

To build this new platform, we will need to overcome key limitations and achieve three main goals:

1. Develop and optimize method(s) to select modalities that accurately profile tissue in a given state.

1a. The method(s) should quantitatively assess the value of a set of integrated modalities for predicting different tissue and disease states.

1b. The method should be demonstrably better than expert human judgement with respect to time, cost, resource requirements, and predictive value.

2. Develop new or improve existing individual molecular and structural profiling capabilities, with respect to spatial and/or temporal resolution, number of markers, volume of tissue and/or other assay properties, so as to reveal the states and transitions for the exemplar diseases described in the Platform Demonstration Areas (see full program announcement).

2a. New or enhanced profiling methods should improve one or all of the following in the context of a sample volume of at least 1 mm3:

i. Number of molecular markers or features routinely detected by 10-100x;

ii. Spatial resolution by 5-10x over what is achievable by conventional light microscopy;

iii. Sample processing time by 5-10x.

2b. A key goal is the expansion and linkage of markers and structures, e.g., establishing the relative value and linkage of molecular markers and features derived from an organelle or cell/tissue structure.

3. Develop a platform that integrates multi-scale, multi-modal data from different states and builds models that predict states and transitions. Inclusion of explainable models in the platform is of interest. Performers working in this goal will:

3a. Identify and implement methods to integrate models or knowledge of state gained in Goal 1, ultimately improving the prediction of profiling methods.

3b. Test the platform against the Platform Demonstration Areas at least annually.

3c. Construct an open data resource to share models and datasets, providing a route to integrate contributions from others and/or commercialize advances, as appropriate.

Platform Demonstration Areas. To demonstrate and validate the ‘tissue time machine’, we have chosen to develop, test, and validate our platform in biomedical contexts that are as broad as possible: an infectious disease, tuberculosis (TB), and two different cancers, triple-negative breast cancer (TNBC) and glioblastoma multiforme (GBM). Each represents a current, unmet biomedical challenge and features a complex, dynamic set of cell and tissue states and transitions. See the full program announcement for more information. Advances across models and measures should inform each other to improve and validate predictive markers, environmental influences and optimize the key ingredients necessary for promoting healthy network development. It is not necessary to form a large consortium or team to do this. Synergies and integrated system demonstrations will be facilitated by Wellcome Leap on an annual basis as we make progress together towards the program goals.

Call for abstracts and proposals.

We are soliciting abstracts and proposals for work over 3 years (with a potential additional one-year option). Proposers should clearly relate their work to one or more Platform Goals and indicate which of the Program Demonstration Areas (PDAs) they will participate in. Additional PDAs can be proposed, but all performers must validate their work against at least one of the specified PDAs.

Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit and for-profit organizations. Applicants are encouraged to contact Wellcome Leap about joining its Health Breakthrough Network by executing its MARFA (or CORFA for commercial entities) agreement. Full execution of the Wellcome Leap MARFA is not required for application submission but is required for any award.

Program Director.

Jason Swedlow, PhD has expertise in mechanisms and regulation of chromosome segregation during mitotic cell division and the development of software tools for accessing, processing, sharing and publishing large scientific image datasets. He is co-founder of the Open Microscopy Environment (OME), a community-led open source software project that develops specifications and tools for biological imaging. He earned his PhD in Biophysics from the University of California San Francisco. In 2012, he was named Fellow of the Royal Society of Edinburgh.

Process and timeline

Program announcement.

30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT

15-Day Abstract review round.

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Day 1

Submission deadline: 17 May 2021

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Day 1

Submission deadline: 17 May 2021

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Day 1

Submission deadline:

17 May 2021

7-page abstracts submitted (from individual organizations or teams) that address one or more thrust areas of the program.

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Day 15

Abstract feedback sent: 1 June 2021

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Day 15

Abstract feedback sent: 1 June 2021

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Day 15

Abstract feedback sent:

1 June 2021

All submissions will receive technical and/or programmatic feedback as well as a recommendation to submit or not submit a full proposal.

30 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK

30-Day Full proposal review round.

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Day 45

Submission deadline: 1 July 2021

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Day 45

Submission deadline: 1 July 2021

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Day 45

Submission deadline:

1 July 2021

25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.

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Day 75

Proposal decision sent: 30 July 2021

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Day 75

Proposal decision sent: 30 July 2021

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Day 75

Proposal decision sent:

30 July 2021

All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.

Mechanics of applying

Who is eligible?

Performers from universities and research institutions: small, medium and large companies (including venture-backed); and government or non-profit research organizations are invited to propose. 

To submit an abstract, proposers will be asked to agree to the following:

I understand that the information being disclosed will be reviewed and evaluated independently on behalf of Leap. I am submitting information with the intention that it imposes no confidentiality obligations on Leap. Furthermore, my submission does not breach any confidentiality obligations that I owe to others; there is no legal reason why I cannot submit information; and I am not underage or otherwise legally incompetent. By submitting, I am not granting, other than for the purpose of evaluation, any rights in relation to any patent, copyright or design. I am not relying upon Leap in any way for legal advice, including (but not limited to) whether the contents of my submission can be protected under IP law. I recognize that Leap may already be aware of or funding the same or related efforts as described by my submission. I agree that no contractual obligation or working relationship is being created between myself and Leap by submitting this information. If the submission is deemed of interest, I may be required to sign a further Agreement with Leap so that any confidential information, that is subsequently shared, is protected.

Abstract application steps.

  1. Download guidelines
  2. Download abstract template (and cost and schedule template)
  3. We’ll remind you when the application portal is open ~48 hours before the submission deadline.
  4. Upload your abstract and submit your application before May 17 at 11:59pm ET.
 

More details will be provided for the proposal round of submissions.

Frequently Asked Questions.

If you have questions, please review our FAQ section.

Note: In 2020, mortality due to TB was exceeded by mortality caused by SARS-CoV-2 infection.

[i] International Agency for Research on Cancer. Cancer today. https://gco.iarc.fr/today/home (2020).

[ii] Global tuberculosis report 2020. https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf.

[iii] World Health Organization. Malaria. Malaria https://www.who.int/news-room/fact-sheets/detail/malaria (2020).

[iv] Risom, T. et al. Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer. Nat. Commun. 9, 3815 (2018).

[v] Echeverria, G. V. et al. Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state. Sci. Transl. Med. 11, (2019).

[vi] Sankowski, R. et al. Mapping microglia states in the human brain through the integration of high-dimensional techniques. Nat. Neurosci. 22, 2098–2110 (2019).

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