Lab News

Congratulations to Ambre Sala for her talk during the the Aging and Stress Session at the 23rd International C. elegans Virtual Conference, "Embryo Integrity Regulates Maternal Proteostasis and Stress Resilience".

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Congratulatons to Laura Bott for her poster at the 23rd International C. elegans Virtual Conference, "A multi-modal fluorescent biosensor for monitoring proteostasis in stress and aging”.

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Congratulations to Xiaojing Sui for her poster presentation, "Proteome remodeling: A missense mutation at a time" at the 2021 FASEB Protein Aggregation Conference and for her work to co-organize its satellite conference: NextGen Symposium on Protein Aggregation for early career researchers.

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Welcome to Max Felland! Max is joining the lab for a summer internship from Carleton College.

Congratulations to 2021 graduates Kyoko Kohno and Charlie Stark!

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Congratulations to Cindy Zhao, Claire Morton and Trevor Hintz for being awarded Weinberg College Summer Research Grants!

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Congratulations to Kyoko Kohno for her Senior Piano Recital and for being selected for the Aryeh Routtenberg Prize in Neuroscience!

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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.

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Congratulations to Tessa Sinnige on her appointment as an Assistant Professor with the Bijvoet Centre for Biomolecular Research at Utrecht University in the Netherlands.

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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.

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Congratulations to Ambre Sala for her March 2020 publication, 

Embryo integrity regulates maternal proteostasis and stress resilience in Genes & Development.

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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 Biology

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/.