Congratulations to Ambre Sala for her talk, "Embryo Integrity Regulates Maternal Proteostasis and Stress Resilience", at the 8th Midwest C. elegans Meeting on April 23, 2021.
Congratulations to Tessa Sinnige on her appointment as an Assistant Professor with the Bijvoet Centre for Biomolecular Research at Utrecht University in the Netherlands.
Congratulations to Tessa Sinnige for her paper, Kinetic analysis reveals that independent nucleation events determine the progression of polyglutamine aggregation in C. elegans, published in the March 16, 2021 issue of PNAS.
Congratulations to Ambre Sala for her March 2020 publication,
Embryo integrity regulates maternal proteostasis and stress resilience in Genes & Development.
Congratulations to Kyoko Kohno, senior Neuroscience and Piano Performance double major, who was a awarded an Advanced AYURG for her work on understanding the mechanism of candidate BET inhibitors and HDAC inhibitors by improving the cytosolic protein folding environment.
Congratulations to Xiaojing Sui for her talk, "Proteome remodelling: a missense mutation at a time" at the 26th Annual Midwest Stress Response and Molecular Chaperone conference.
Congratulations to Eirene Fithian, junior Biology major, who was awarded an AYURG for her work on generating tyrosine receptor-based SNAP-Tag probes that could be used to quantify clathrin-mediated endocytosis and protein aggregation.
We study the regulation of the heat shock response and the function of molecular chaperones to maintain the functional health of the proteome and lifespan. Our current interests are: to understand how different tissues in C. elegans sense diverse forms of environmental and physiological stress and communicate proteotoxic stress signals between tissues, to determine the mechanism by which proteostasis collapse occurs in aging, to establish genetic and small molecule approaches to reset the heat shock response and other cell responses that fail in aging and disease, and to prevent proteotoxic stress in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS and other protein folding disorders.
The Proteostasis Network
Protein Quality Control (PQC) is regulated by the Proteostasis Network (PN) that controls protein synthesis, folding, transport and degradation of all proteins to ensure their stability and function. We study the properties and regulation of cell stress responses, molecular chaperones, the ubiquitin-proteasome and autophagy-lysosome system at the organismal level using C. elegans and in patient derived induced neurons to examine the mechanisms of proteotoxicity in cells and tissues against proteotoxic damage.
Aging is associated with the appearance and accumulation of non-native proteins with folded states that are highly aggregation-prone and amyloidogenic. We are interested in the molecular basis of quality control failure in aging, that we have termed Proteostasis Collapse, which is associated with a functional decline in specific arms of the PN leading to protein aggregation.
Proteostasis in Neurodegenerative Diseases
Alzheimer's disease, ALS, Parkinson's disease, Huntington's disease, Frontal Temporal Dementia and other neurodegenerative diseases are all associated with age-dependent protein aggregation and cellular dysfunction. We have used both C. elegans and induced neurons to discover how protein misfolding and aggregates interferes with cellular function and to discover small molecules that enhance chaperone expression and function.
The Heat Shock Response
All cells (and organisms) respond to environmental stress such as elevated temperatures and other abiotic stressors by activation of HSF1 and selective transcriptional activation of molecular chaperones and other components of the PN. In isolated cells in tissue culture, the heat shock response (HSR) is regulated cell autonomously but in C. elegans, the HSR is regulated cell non-autonomously by the AFD sensory neuron to confer cellular healthspan and lifespan.
The Proteostasis Consortium
We share an NIH Program Project Grant from NIA on Proteostasis of Aging and Neurodegenerative Diseases together with Judith Frydman (Stanford), Jeff Kelly (Scripps), Steve Finkbeiner (UCSF), and Dan Finley (Harvard). Additional information on our research and the Proteostasis Consortium Wednesday Seminars be found at https://www.proteostasisconsortium.com/.