Mol Bio Colloquium

Mol Bio Graduate Colloquium
Feb 17, 2023, 4:00 pm4:00 pm
Thomas Laboratory, 003
Free and open to the university community and the public.


Matthew Tyl
Graduate Student
Cristea Lab
Morgan Stevenson
Postdoctoral Fellow
Murphy Lab


Event Description


February 17, 2023






Cristea Lab


Lysine acylation links cellular metabolism to immune signaling during viral infection


Cellular survival relies on phenotypic plasticity in response to changing conditions. Information on cellular state is transmitted through addition or removal of post-translational modifications (PTMs) onto histones to alter gene expression through epigenetic regulation. Further, these same PTMs decorate the entire proteome, serving as a rapid toggle of protein function. Nearly all proteins which add and remove PTMs—as well as the PTMs themselves—depend on crucial cellular metabolites (acyl-CoA’s, NAD+, ATP, etc.). The fluctuations of these metabolites indicate the metabolic status of the cell, enabling proper adaptation of the proteome. Here, I focus on how two products derived from the endpoint of glycolysis—acetyl-CoA and lactate—serve as metabolic signals during viral infection via the direct addition onto proteins as PTMs. I address how the evolutionarily conserved protein sirtuin 6 (SIRT6) achieves an antiviral function through regulation of protein acetylation. By performing the first unbiased search for SIRT6 substrates, I gain insights into enzyme-substrate relationships that may enable this antiviral function. Next, I report the first global analysis of the novel lysine PTM, lactylation, during infection with a pathogen. I found an intriguing enrichment for this lactate-derived PTM on intrinsically-disordered regions of proteins, as well as an upregulation on immune signaling proteins during a state of active viral replication. These findings illuminate how changes to glycolytic flux during viral infection induce rapid cellular responses via the dynamic regulation of PTMs, with likely implications to other disease states characterized by dysregulation of cellular metabolism, such as cancer, aging, and autoimmune disorders.






Murphy Lab


EGL-30/GNAQ activation rejuvenates age-related cognitive decline in worms and mammals  


Age-related cognitive decline is experienced broadly across the animal kingdom, and model organisms such as C. elegans provide a unique tool for identifying the mechanisms of decline and potential memory-improving interventions. We previously showed that expression of gain-of-function Gαq/egl-30 exclusively in aged animals is sufficient restore long-term associative memory in worms experiencing cognitive decline. Since EGL-30/GNAQ and Gαq signaling pathways are highly conserved between worms and mammals, we wondered whether this pathway plays a similar role in mammalian cognitive decline. We found that GNAQ is enriched in excitatory neurons in the mouse hippocampus, and its expression declines with age. Next, we tested whether expression of GNAQ gain-of-function could similarly improve memory in aged mice; GNAQ gain-of-function overexpression in hippocampal neurons of 24-month-old mice significantly improved long-term memory, suggesting that increased GNAQ function is sufficient to rescue memory in aged animals. Single-nucleus RNAseq showed cell autonomous and cell non-autonomous changes in genes related to synaptic function and learning and memory pathways. We then tested worm orthologs of mouse genes upregulated by GNAQ(gof) overexpression for functional roles in EGL-30/GNAQ-dependent enhancement of worm memory; several genes were found to be critical for improved memory. These findings demonstrate that EGL-30/GNAQ is a conserved regulator of age-related cognitive decline, with therapeutic potential to cognitive aging.

Department of Molecular Biology
Event Category
Graduate Student Colloquium