the Levine Research Group at the Yale School of Medicine (LRG@ysm) seeks to biophysically characterize human degenerative disorders in the context of aging using computational and experimental techniques.

In particular, we work to understand protein aggregation and dysfunction over the lifecourse. Disparate age-related disorders often involve a toxic accumulation of amyloid oligomers and plaques that result in cellular dysfunction and death. The inability to regulate promiscuous protein oligomers is also a notable hallmark of human aging, where proteostasis gradually declines with age. By combining molecular models of protein folding and aggregation with single molecule fluorescence tools, we can deduce and modify thermodynamic landscapes that lead to pathological outcomes.

For more information, check out our research interests and publications pages!

PI: Zachary A. Levine, Phd

Zachary (Zach) Levine is currently an Assistant Professor of Pathology and Biophysics at the Yale School of Medicine. His training in computational biophysics has allowed him to leverage protein folding predictions to better understand solution and cellular biophysics, especially in the context of pathological plaques and oligomers that affect human aging and disease.

Read more

Single Molecule Fluorescence

Reversible (liquid) and irreversible (solid) protein oligomers drive a multitude of physiological and pathological events. However, the inability to regulate promiscuous and long-lived proteinaceous complexes results in a wide variety of debilitating diseases, including amyloid disorders such as Alzheimer's Disease and Diabetes. These same species potently induce cellular senescence and are strongly coupled to aging pathways, making them an attractive target for senolytics or related therapeutics. Our group utilizes single molecule fluorescence techniques such as single-molecule FRET (smFRET) to identify heterogeneous oligomers that are difficult to resolve with ensemble methods. Our focus on single molecules also allows us to make comparisons to molecular simulations and synergistically bridge in silico and in vitro observations.

protein folding

We're particularly interested in modeling intrinsically disordered proteins (IDPs) through molecular dynamics (MD) simulations in order to characterize physiological and pathological protein states. IDPs, which make up over a third of the human proteome, are challenging to study experimentally because of their lack of secondary structure, however computational techniques are capable of directly measuring the superposition of states that IDPs inhabit.

Solution biophysics

Theoretical predictions are then combined with observations from solution NMR spectroscopy, chromatography, and immunoassays in order to iteratively refine models and recapitulate the molecular basis of amyloid diseases.

LRG@YSM IS always searching for enthusiastic and motivated scientists to join our team!

Created in the Fall of 2019, we are currently expanding and are interested in recruiting undergraduate, graduate, and postdoctoral researchers. For more information, please send your CV to:

Recent News

One of our articles was recently featured on the front cover of the Journal of the American Chemical Society (JACS)! Check out more information here.