What causes proteins to age, and do old proteins affect our health? If we could measure each ingredient of overall nutrition inside individual cells, how much more could we understand about metabolism and its link to disease?

Eight new projects are now underway developing technologies and designing approaches to answer these broad questions in biology, carried out by 16 new Allen Distinguished Investigators:

• Alexander Aulehla, M.D., Ph.D., European Molecular Biology Laboratory

• Abhishek Chatterjee, Ph.D., Boston College

• Tim Clausen, Ph.D., Research Institute of Molecular Pathology

• Alf Honigmann, Ph.D., Technische Universität Dresden

• Meritxell Huch, Ph.D., Max Planck Institute of Molecular Cell Biology and Genetics

• Janine Kirstein, Ph.D., University of Bremen

• Lydia Kisley, Ph.D., Case Western Reserve University

• Yi Lu, Ph.D., University of Texas at Austin

• Gary CH Mo, Ph.D., University of Illinois Chicago

• Niculina Musat, Ph.D., Helmholtz Centre for Environmental Research – UFZ Leipzig

• André Nadler, Ph.D., Max Planck Institute of Molecular Cell Biology and Genetics

• Laura Sanchez, Ph.D., University of California, Santa Cruz

• Mikhail Savitski, Ph.D., European Molecular Biology Laboratory

• Bilal Sheikh, Ph.D., Helmholtz Munich

• Hryhoriy Stryhanyuk, Ph.D., Helmholtz Centre for Environmental Research – UFZ Leipzig

• Eranthie Weerapana, Ph.D., Boston College

The Paul G. Allen Frontiers Group, a division of the Allen Institute, today announced eight awards of up to $1.25 million each to fund research projects led by these 16 investigators. Together, these awards represent a total of approximately $10 million in funding from the Paul G. Allen Family Foundation, as recommended by the Frontiers Group, to support cutting-edge, early-stage research projects that promise to advance the fields of biology and medicine. 

The eight awarded projects were selected from open calls for proposals in two fields: nutrient sensing and protein lifespan, areas that were selected from an open call for topics through a 2021 campaign called “Ask Anything, Change Everything.” To choose research areas that they recommend for funding, the Frontiers Group looks for emerging fields where an investment could be catalytic to advance scientific progress — not just for awardees, but for all in that particular field.

“When we launched our campaign “Ask Anything, Change Everything” to identify key — but currently unmeasurable — biological metrics, the feedback from the research community was overwhelming, and their ideas catalyzed this pioneering initiative. These newest awardees bring bold technological approaches to capture essential but unknown aspects of our biological machinery. Their work could not only change how we view fundamental biology, but also upend how we think about health and disease,” said Kathy Richmond, Ph.D., M.B.A., Executive Vice President and Director of the Frontiers Group and the Office of Science and Technology at the Allen Institute.

The Allen Distinguished Investigator program was launched in 2010 by the late philanthropist Paul G. Allen to back creative, early-stage research projects in biology and medical research that would not otherwise be supported by traditional research funding programs. Including the new awards, a total of 130 Allen Distinguished Investigators have been appointed during the past 12 years. Each award spans three years of research funding.

Meet the new Allen Distinguished Investigators

Nutrient sensing

Researchers in this cohort are developing new technologies to measure or visualize nutrient levels within cells. Their work addresses a key need in the field, namely the ability to capture detailed information about metabolites, chemical compounds and other nutrients in live individual cells. These new techniques could propel understanding of the basic biology of cells as well as how metabolism or nutrition processing goes wrong in diseases like diabetes or malnutrition.

Lydia Kisley, Ph.D. 
Case Western Reserve University 
Laura Sanchez, Ph.D. 
University of California, Santa Cruz 

Right now, there’s no good way to measure the distribution of nutrients inside individual cells. Lydia Kisley and Laura Sanchez are leading the development of a technique to address this problem by physically expanding cells — picture a cell stretched on silly putty — and capture details of nutrient location and amount in those cells. Their new method is called Expansion Mass Spectrometry and the scientists plan to use it to study nutrients in and around ovarian cancer cells to better understand metabolism in these cancer cells and how cells’ local environments influence nutrient location and amounts.

Yi Lu, Ph.D.
University of Texas at Austin 

Yi Lu is leading a project to engineer DNA molecules in a variety of ways to detect and visualize nutrients in single cells. Because nutrients are often very small molecules — think individual sodium ions or sugar — it’s very difficult to capture them under a microscope using standard methods, and even methods that can detect small nutrient molecules have difficulty separating out nutrients of similar sizes. Lu’s technique aims to light up individual nutrients with DNA fluorescent sensors; the team will also develop methods to send these sensors to different parts of the cell simultaneously to visualize multiple metabolic reactions in the same cell.

André Nadler, Ph.D.
Meritxell Huch, Ph.D. 
Max Planck Institute of Molecular Cell Biology and Genetics 
Alf Honigmann, Ph.D. 
Technische Universität Dresden 

Our bodies rely on fats and their molecular cousins, collectively known as lipids. These slippery molecules construct our cell walls and store 90% of our energy, and their dysregulation is associated with diseases like diabetes and fatty liver disease. André Nadler, Meritxell Huch and Alf Honigmann are leading a project to apply a technology they developed to visualize lipids in cells using fluorescence microscopes. They’re now using this technique to study the turnover and transport of lipids in laboratory models of the two main organs for nutrient uptake and processing, the intestine and the liver.

Bilal Sheikh, Ph.D.     
Helmholtz Munich 
Niculina Musat, Ph.D.  
Hryhoriy Stryhanyuk, Ph.D.    
Helmholtz Centre for Environmental Research – UFZ Leipzig 

Our cells are incredibly diverse. Visualising the metabolism of individual cells is critical to understanding how our organs and body work. However, metabolic reactions happen in milliseconds in areas 50 times thinner than a human hair. Bilal Sheikh, Niculina Musat and Hryhoriy Stryhanyuk are developing a new technology dubbed Meta-SCOPE to visualize metabolism in single cells, shedding light on important but to-date invisible cellular processes.

Protein lifespan

Proteins are the building blocks of life — nearly all cellular structures and processes are built and carried out by proteins. Do our proteins age like our bodies age? While scientists have discovered how cells turn over old proteins to create new forms, it’s not clear how lifespan varies among different kinds of proteins, what it means to have “old” proteins, or how the cellular environment could affect protein aging. Researchers in this cohort are building new technologies and designing experiments to address important questions around protein lifespan and aging.

Abhishek Chatterjee, Ph.D.
Eranthie Weerapana, Ph.D. 
Boston College 

While techniques exist to capture the entire suite of proteins in an individual cell — also known as a proteome — it’s still difficult to capture the dynamics of protein synthesis and degradation on a large scale. To understand the variation of protein lifespan in the context of the entire proteome, Abhishek Chatterjee and Eranthie Weerapana are developing new technologies to tag and measure newly created proteins at specific timepoints. They’ll use this technique to study protein lifespan in a type of immune cell known as a T cell.

Janine Kirstein, Ph.D. 
University of Bremen 
Tim Clausen, Ph.D. 
Research Institute of Molecular Pathology  

Janine Kirstein and Tim Clausen are building a “protein lifespan” kit to carefully track the complete life cycle of a single protein. They’ll use a specially designed fluorescent tag to monitor the creation, maturation, aging and degradation of a single muscle protein, myosin, in the microscopic worm C. elegans. They are also tracking mutated versions of myosin known to cause neuromuscular disease in humans, to understand how protein aging, misfolding and other aspects of protein lifespan might play a role in these diseases.

Gary CH Mo, Ph.D.
University of Illinois Chicago 

Current techniques to access and understand large numbers of proteins from individual cells involve mechanically or chemically breaking cells open. These disruptive methods kill cells and can significantly muddle the very biological processes researchers aim to study. Gary Mo is developing “nano-scalpels” to precisely extract proteins from cells. This relies on a newly discovered method to reverse pore formation on the cellular plasma membrane. Mo and his team will make these pores open and close on demand, allowing them to take tiny biopsies from inside cells. By keeping cells functioning throughout such operations, they aim to follow and reveal the key features of proteomic balance within living cells.

Mikhail Savitski, Ph.D.
Alexander Aulehla, M.D., Ph.D. 
European Molecular Biology Laboratory  

Some proteins, like those in the lenses of our eyes, are as old as we are, while some proteins are created and degraded much more rapidly. How do cells know how old their proteins are, and how do they decide when to replace them? To understand these vast differences in protein aging and lifespan, Mikhail Savitski and Alexander Aulehla are leading a project to ask whether certain modifications on proteins mark their age or target them for turnover.