Andrew Gellman, Huaiying Zhang Receive Kaufman Foundation Awards
"Charles Kaufman was a visionary in recognizing that collaborative and interdisciplinary research could lead to huge quality-of-life improvements across the landscape of human experience," said Lisa Schroeder, president and CEO of The Pittsburgh Foundation in announcing the grants. "He committed his philanthropy to our foundation to ensure that what was funded followed that vision, and I believe these grants are evidence that the Scientific Advisory Board has done just that. The funded projects offer real prospects for breakthroughs."
Under the New Initiatives Award, Gellman and his collaborator David Waldeck, a professor of chemistry at the University of Pittsburgh, will study and manipulate chiral molecules via application of magnetic fields, with the goal of using this understanding to improve production of chiral pharmaceuticals. The proposed project, "Spin chemistry as the basis for enantioselective surface chemistry," aims to demonstrate and understand the influence of magnetic fields on the enantiospecific interactions of chiral molecules with magnetic surfaces. Ultimately, this phenomenon can be used to develop new chemical processes that differentiate between enantiomers.
Much like a pair of hands, chiral molecules exist in two structures, known as enantiomers, that are mirror-images of one another. The problem is that many important pharmaceuticals are chiral molecules that are synthesized as mixtures of both enantiomers. However, life on Earth is homochiral, meaning that all sugars, DNA, amino acids, and proteins exist in only one of their two enantiomeric forms. The consequence is that when chiral pharmaceuticals are administered without consideration of their "handedness," one enantiomer may be therapeutic while the other is toxic — as in the infamous case of thalidomide. The aim of Gellman's project is to explore and develop a new approach that will enable direct synthesis of the therapeutic enantiomer alone.
Zhang researches the physics and chemistry of liquid condensation in live cells, which could inform the development of new treatments for cancer.
Human cells are organized into functional compartments called organelles. Most organelles, like the nucleus and mitochondria, are encased by lipid membranes. Others, like stress granules and nucleoli, do not have a membrane. In the last decade, researchers have discovered that these membrane-less organelles are condensed liquid droplets formed by liquid-liquid phase separation.
Zhang has developed optogenetic tools that control genetically engineered proteins using light to study how condensation occurs within the complex cellular environment and the role it plays in cellular function. Specifically, Zhang uses these tools to study membrane-less organelles called APBs that are associated with telomeres in some cancer cells. Telomeres, the protective endcaps of chromosomes, play an important role in cancer. In normal cells, telomeres shorten over the cells' life span and when they reach a certain length, they trigger cell death. In cancer cells, telomeres maintain their length, allowing the cancer cells to live indefinitely.
Under the $150,000 New Investigator Award from the Kaufman Foundation, Zhang will attempt to determine the physics that underlies APB condensation and the chemistry behind the formation of APB and its material properties. Her interdisciplinary research stands to reveal insights into the foundational physics and chemistry of phase separation in live cells. It may also yield important information that will allow researchers to manipulate conditions within the cell to determine how APB condensation and properties can be altered to prevent telomere elongation, which could lead to new avenues of research in cancer therapy.
Grants from the Kaufman Foundation, a supporting organization of the Pittsburgh Foundation, go to institutes of higher learning in Pennsylvania for scientists pursuing research that explores essential questions and/or crosses disciplinary boundaries. New Investigator grants are awarded to scientists transitioning to independent appointments and are meant to empower promising scientists at the beginning of their careers. New Initiatives grants are awarded to investigators with a strong record of accomplishment who are pursing innovative interdisciplinary approaches to a research question.