Rice Institute for Biomedical Research
Department of Molecular Biosciences
Northwestern University
Lab News
Former Morimoto Lab
post-doc, Tali Gidalevitz,
visited and couldn't resist
doing a bit of nostalgic work
at her old bench.
Congratulations to Anan Yu for
her first co-authored
publication in Cell Stem Cell,
Recapitulation of endogenous
4R tau expression and
formation of insoluble tau in
directly reprogrammed human
neurons
Postdoctoral Fellow, Thomas
Stoeger, met up with Alex
Rodriguez Gama, who will be
joining the Morimoto Lab as a
Postdoctoral Fellow later in
2022, at the National Institutes
of Health Trainees meeting in
Bethesda, MD.
Congratulations to Morimoto
Lab graduating seniors Claire
Morton and Eirene Fithian!
They were awarded honors at
the 2022 Senior Thesis and
Awards Celebration on June 1.
Eirene also won the David
Shemin Prize for Basic
Research for her senior honors
thesis.
Investigating the Link between
stress resilience and lipid
metabolism and in the cbd-1
mutant in C. elegans
Claire Morton (Biology;
Chemistry minor)
Mentor: Ambre Sala
Establishing A Quantitative
Proteostasis Probe for
Neuronal Signaling Receptor
Trafficking Upon Protein
Aggregation
Eirene Fithian (Biology;
Science in Human Culture)
Mentor: Anan Yu
Congratulations to Xiaojing
Sui for receiving a Post-
Doctoral Fellowship from the
National Ataxia Foundation.
Congratulations to Laura Bott
for her talk, A metastable
protein conformational switch
reveals cell state transitions in
aging and stress at the 27th
Annual Midwest Stress and
Molecular Chaperone Meeting
in January 2022.
Congratulations to Laura Bott
for her talk, A metastable
protein conformational switch
reveals cell state transitions in
aging and stress, at the
Chicago Area Worm Meeting
in December 2021.
Happy Holidays from the
Morimoto Lab to you! View
pictures of our holiday party
here.
Congratulations to Rogan
Grant for his article in Nature,
Circuits between infected
macrophages and T cells in
SARS CoV-2 pneumonia
Congratulations to Ambre
Sala for her article in Trends in
Cell Biology, Protecting the
future: balancing proteostasis
for reproduction
Congratulations to Laura Bott
for her talk, A metastable
protein conformational switch
reveals cell state transitions in
aging and stress, at the Young
Scientist Symposium on
Protein Quality Control on
September 24, 2021!
The lab held the annual
Morimoto Open in August
and this year's champion was
Thomas Stoeger. Max Felland
was the Runner Up.
Congratulations to everyone
for their well-played matches.
View more photos of the
Morimoto Open here.
The annual Undergraduate
Symposium took place in
August with undergraduate
students presenting their
summer research.
Max Felland and Cindy Zhao
pictured.
![MWSM_horizontal_FINAL[2].jpg](https://static.wixstatic.com/media/594a6c_287aace1a6c748ef86cd356c1a4479e1~mv2.jpg/v1/fill/w_328,h_193,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/MWSM_horizontal_FINAL%5B2%5D.jpg)
![Undergrad symposium_May2 022[35].jpg](https://static.wixstatic.com/media/594a6c_2574a7ff3e4a4546ae27c4370c34605c~mv2.jpg/v1/fill/w_328,h_437,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/Undergrad%20symposium_May2%20022%5B35%5D.jpg)
We study the regulation of the heat shock response and the function of molecular chaperones and the proteostasis network to maintain the functional health of the proteome, to ensure optimal cellular health and to promote longevity. 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 organismal health, to determine the mechanisms by which proteostasis collapse occurs in aging and the relationship between proteostasis failure and other markers of aging. These observations are used to study cell stress responses and proteostasis in patient-derived direct differentiated neurons to develop small molecule strategies to restore the proteostasis network to delay or prevent proteome mismanagement that occurs in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS and other protein folding disorders.
C. elegans viewed through the microscope at the Morimoto Lab
Dr. Rick Morimoto and Lab Manager, Sue Fox, celebrate the graduation of Charlie Stark and Kyoko Kohno in June 2021.
C. elegans viewed through the microscope at the Morimoto Lab
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/.