Uncovering Human Health, One Cell at a Time

Philanthropy steps in to expand the Human Cell Atlas through a new RFA

By Jonah Cool, Chan Zuckerberg Initiative Science Program Manager, and Jessica Langer, Helmsley Charitable Trust Program Officer, Crohn’s Disease

Fluorescent image of Madin-Darby Canine Kidney (MDCK) cells. These cells are used to study cell polarity, motility, and cell-cell adhesions. Photo by Jobelle Peralta.

We like to think of us humans as comprising more than just skin and bones, but rarely do we consider this: We are composites of more than 30 trillion cells. Cells are the fundamental units of life, and yet we know very little about them on an individual level. This is the next frontier in understanding human health.

We are experiencing a transformative moment in biology, when novel technologies make it possible for scientists to isolate single cells and define the unique features of thousands of cells at once. Dr. Sarah Teichmann and Dr. Aviv Regev recognized the promise of these technologies for mapping the human body, and began to rally international, cross-disciplinary interest, along with financial support from both private and government funders to create a new fundamental biological reference.

Their vision has a name: the Human Cell Atlas (HCA), a global, scientist-led effort that aims to map all the cells in the human body. This is an ambitious goal, and one that can underpin the next wave of medical advancements by detailing all the cell types that comprise us. This work will help explain how cells develop and collectively form tissues, and so much more. Most relevant for biomedical researchers, the HCA will begin to teach us how specific cells contribute to disease. This will lead to better diagnoses, monitoring, and treatment of countless diseases — particularly those that remain poorly understood, like Crohn’s disease.

The Chan Zuckerberg Initiative (CZI) and the Helmsley Charitable Trust — aware of both the legacy and responsibility of philanthropy in supporting great scientific endeavors — are excited to contribute to the HCA through two new Requests for Applications (RFA). These grant opportunities are open to scientists around the world and aim to spur more collaborations to grow the HCA.

Scientists work in the labs at the Chan Zuckerberg Biohub in San Francisco. Photo by Chan Zuckerberg Initiative.

Creating a Gut Cell Atlas

Helmsley is committed to improving the lives of Crohn’s disease patients, and mapping each cell in the gut at high resolution is an important step to advance this goal. Creating a Gut Cell Atlas (GCA) will help us understand how these cells interact, function and change during disease and potentially lead to better treatments for patients.

Helmsley has long supported efforts to study genetics of Crohn’s disease. To date, the field has successfully identified over 200 regions of the genome associated with the disease. A Gut Cell Atlas will help us understand exactly where and how the genes in these regions are active at the cellular level, providing insight into how they function, both in healthy individuals and in patients with Crohn’s disease. This will be key to advancing precision medicine — tailoring the right treatment to the right individual — which we believe is the way forward for Crohn’s disease and countless other chronic conditions.

Helmsley seeks to fund projects that will contribute collectively to the GCA, effectively cataloguing the many cell types in the gut and the myriad connections among them. We invite investigators to bring their diverse expertise and innovative technologies to this effort. What’s also exciting about the GCA is the promise it holds as a model for building other comprehensive organ system atlases.

Bringing together diverse experts

CZI’s Seed Networks RFA will continue the growth and progress of the HCA community, providing a way for new groups to contribute to the HCA. This opportunity is open to researchers in any country or specialty and focuses on technology. Notably, at least one member of each Seed Network must be a software engineer or computational biologist, reflecting CZI’s commitment to fostering diverse teams to work on foundational problems.

In fact, part of what makes the HCA exciting is the intersection of technology and science. For all the medical advancements of the past century, human cell biology has not been extensively studied, let alone with nascent technologies that push the limits of analysis. Creating the HCA demands that we first learn to manage, analyze and integrate large volumes of data types — a complex challenge requiring input from top minds across fields (tech, data, tissue specialists, and clinicians to name a few) and from around the world.

CZI grantees working on the Human Cell Atlas share their learnings at a poster session during CZI’s West Coast meeting.

A high-quality atlas should be openly accessible, and a data platform for the HCA will be more than an archive — it will give cloud access to researchers everywhere. Scientists and non-scientists alike will be able to use and explore the HCA. This central platform will help unify the diverse scientific efforts that will likely arise from the GCA and Seed Networks projects.

The HCA will help us understand fundamental questions about cell biology, disease progression, cellular state, and many more areas. Already, the HCA is starting to make a difference in our understanding of conditions such as cystic fibrosis and kidney disease.

As funders, CZI and Helmsley are excited to support the continued growth of this vibrant community of scientists. The HCA offers great potential to uncover many mysteries of human health. While we don’t know exactly what will result from the HCA, our responsibility in philanthropy is to take risks and invest in advancing this next frontier of science.

Jonah Cool, Science Program Manager, Chan Zuckerberg Initiative

Jonah Cool is a cell biologist and geneticist by training, and is currently a program manager at the Chan Zuckerberg Initiative, where he leads the organization’s efforts to support the international Human Cell Atlas consortium. He was an American Heart Association fellow while completing his PhD at Duke Medical Center, with a focus on the role of vascularization during cell differentiation and organ morphogenesis, and was subsequently a Ruth Kirchstein Fellow at the Salk Institute studying nuclear organization during stem cell differentiation. Dr. Cool previously worked in intellectual property litigation, as well as ran an industry research group working toward therapeutic application of 3D bioprinted human tissue. He has a deep love of cell biology and, in particular, the origins of cellular heterogeneity and how diverse cells assemble into complex tissues.

Jessica Langer, Program Officer, The Leona M. and Harry B. Helmsley Charitable Trust

Dr. Jessica Langer is a Program Officer for the Helmsley Charitable Trust’s Crohn’s Disease Program. Jessica helps to manage the program’s research grants portfolio and to identify new opportunities with a focus on finding novel therapeutics and innovative new strategies to improve the quality of life for Crohn’s disease patients. Before joining Helmsley, Jessica was an associate principal scientist at L’Oreal, where she was responsible for setting up external collaborations in the areas of skin biology and safety testing, as well as the manager of an internal research lab focused on the study of human skin. Previously, she worked at Chromocell, a start-up biotechnology company, specializing in creating complex cell lines for compound screening. Jessica received her Ph.D. from Mt. Sinai School of Medicine in Mechanism of Disease Therapy and completed a post-doctoral fellowship in the same lab focused on immunology and aging.

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Chan Zuckerberg Initiative Science

Supporting the science and technology that will make it possible to cure, prevent, or manage all diseases by the end of the century.