One scientist has a big idea to improve stem cell therapies for a broad range of diseases. Another wants to study how our gut cells talk directly to our brains — and how that communication might go awry in Parkinson’s disease. A third has a plan to examine how what we eat impacts our bodies at the level of our individual cells.

These are some of the bold ideas behind the five newly selected Allen Distinguished Investigator awards announced today by The Paul G. Allen Frontiers Group, a division of the Allen Institute, supporting new projects that will advance knowledge about our cells and tissues in health and disease.

“The field of stem cell biology has the potential to change how we treat diseases by helping precision medicine, and there’s so much we still don’t understand about the interplay between cells in living tissues or organs,” said Kathy Richmond, Ph.D., M.B.A., Director of the Frontiers Group. “Our 2019 Allen Distinguished Investigators are pushing their fields in these two areas, through new technology development, probing pivotal interactions in the body that cause health to fail, and generating creative new stem cell models that will improve our understanding of different human diseases.”

Each award confers $1.5 million in research support over three years, for a total of $7.5 million in funding for studies of human diseases using stem cells and the development of new technologies to examine single cells in tissues, such as the gut. The Frontiers Group, launched by the late philanthropist Paul G. Allen, directs funding to researchers around to world whose work has the potential to accelerate scientific discoveries or launch entirely new avenues of exploration.

“This award is enabling us to take a big risk in our arena by generating a completely new technology, one which will be useful to the scientific community. That’s really exciting for us,” said Samantha Morris, Ph.D., who is one of the newly selected Allen Distinguished Investigators and an Assistant Professor at Washington University in St. Louis. Morris will lead a team working to generate a “blueprint” that maps how stem cells develop into other types of cells, such as kidney or brain cells, using cells from the Allen Cell Collection, a set of gene-edited human stem cell lines generated by researchers at the Allen Institute for Cell Science, another division of the Allen Institute.

The Allen Distinguished Investigator program began in 2010 to support early-stage research that is less likely to receive support from traditional funding sources, but which has the potential to significantly advance our understanding of biology. With the 2019 awards, there are a total of 74 Allen Distinguished Investigators appointed since the program’s inception.

Three awards were given to researchers using human stem cells to model disease and advance our understanding of human health. Morris’ project aims to address a stumbling block that can help anyone using human stem cells to study disease or basic biology, while the other two projects will address pressing questions about Parkinson’s disease and nutrient absorption, an area that could have implications for malnutrition and obesity.

Two awards were given to researchers developing technologies to study molecules at the single-cell level in the context of tissues. While researchers have uncovered many aspects of basic cell biology by studying cells in a petri dish, studies of cells in their native environments — in a tissue or whole organ — will allow scientists to capture the cues and signals unique to this natural context, the cells’ so-called microenvironment.

Meet the 2019 Allen Distinguished Investigators

Samantha Morris, Ph.D.
Washington University in St. Louis
Researchers have been working for years to develop stem cell therapies that could repair or replace diseased organs, but spurring human stem cells to develop into healthy, mature types of cells in the lab has proven difficult. Samantha Morris aims to create a “blueprint” of cell identity that will enable researchers to improve the way they generate different kinds of cells from human stem cells, with the ultimate goal of delivering on the promise of stem cell therapy.

Joshua Rabinowitz, Ph.D.
Princeton University
We know a great deal about how the body processes food, but relatively little about how metabolism varies across individual cells of the body. Joshua Rabinowitz will lead a team developing new technologies to study metabolites, the molecules that result from our bodies’ conversion of food into energy, and metabolic activity in single cells in mouse and human tissue. His work could ultimately shed new light on human diseases that involve altered metabolism, such as diabetes, cancer and heart disease.

Clive Svendsen, Ph.D.
Cedars-Sinai 
Human intestines and their beneficial bacteria — our gut microbiome — interact directly with the brain, but it’s unclear what role these interactions might play in disease. Clive Svendsen aims to test how this gut-brain axis and the microbiome might influence neuron death in Parkinson’s disease, a devastating neurodegenerative disorder that affects millions of people around the world. Svendsen will lead a team using stem cells from patients with the disease to model the gut-brain axis and the role of the gut microbiome in Parkinson’s disease.

Savas Tay, Ph.D.
University of Chicago
In recent years, researchers have developed new techniques to study genes and their output, or gene expression, in single cells in the context of tissues or organs. Savas Tay is leading a team to develop a method that combines the study of gene expression at the level of individual cells with single-cell measurements of proteins and protein complexes, using samples of healthy and diseased gut tissue from patients with Crohn’s disease, an auto-immune disease that causes chronic inflammation of the intestines. Capturing the variation of all these molecules in individual cells could lead to new understanding of Crohn’s and other diseases.

James Wells, Ph.D.
Cincinnati Children’s Hospital Medical Center 
Jim Wells will lead a team studying a rare type of intestinal cell known as enteroendocrine cells that sense nutrients from the food we eat and then control how nutrients are absorbed and stored. Wells’ team will use stem cells from patients with genetic disorders affecting their ability to absorb nutrients to study these cells in the lab. Understanding more about enteroendocrine cells, which produce hormones that regulate our ability to process food, could pave the way for new therapies for malnutrition and diseases like Type 2 diabetes.

About The Paul G. Allen Frontiers Group

The Paul G. Allen Frontiers Group, a division of the Allen Institute, is dedicated to exploring the landscape of bioscience to identify and foster ideas that will change the world. The Frontiers Group directs funding through award mechanisms to accelerate our understanding of biology, including: Allen Discovery Centers at partner institutions for leadership-driven, compass-guided research; and Allen Distinguished Investigators for frontier explorations with exceptional creativity and potential impact. The Paul G. Allen Frontiers Group was founded in 2016 by the late philanthropist and visionary Paul G. Allen. For more information, visit allenfrontiersgroup.org.