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Principal Investigator: David Allan Drummond
Organization: UNIVERSITY OF CHICAGO
Fiscal Year: 2024
Award: $120,900
Funding agency: National Institute of General Medical Sciences
Project Summary from the Parent Award
A conceptual and empirical revolution is occurring in our understanding of the eukaryotic heat-shock response.
Heat shock has long been conceived of as a proteotoxic stress, triggering formation of toxic aggregates of
denatured proteins, which must be cleaned up by induced heat shock proteins. Recent results from our group
and others have established a complementary paradigm: temperature acts as a physiological signal, triggering
the adaptive formation of biomolecular condensates with specific cellular functions, and the condensation
process is regulated by heat shock proteins. Crucially, in the proteotoxic model, aggregates are trash, but in the
adaptive condensation model, they are functional treasure. Using an integrated set of biochemical, cell biological,
and evolutionary approaches established over the past decade, we are pursuing three linked areas: 1) identifying
and dissecting the cellular functions of particular heat-shock and stress-induced condensates of protein and
mRNA; 2) studying the regulation of condensation and dispersal, focusing on the specificity of physiological
condensates and their remodeling and reversal by stress-induced molecular chaperones; and 3) probing the
sensation and transduction of temperature into adaptive responses in fungi which rely on warm-blooded hosts
for growth or dispersal, and in the temperature-dependent activation of cells in the vertebrate immune system
during fever. In addition to fundamental insights into the operation and organization of eukaryotic cells, these
studies promise to shed light on intracellular aggregation processes known to be dysregulated during
neurodegenerative disease, uncover new mechanisms for the control of fungi, and provide new molecular insight
into how fever promotes immune-cell activation.
Terms: <Area><Biochemical><Biochemistry><Biological><Biological Chemistry><Budding Yeast><Cell Body><Cell Communication and Signaling><Cell Function><Cell Physiology><Cell Process><Cell Signaling><Cells><Cellular Function><Cellular Physiology><Cellular Process><Cellular biology><Chaperone><Degenerative Neurologic Disorders><Endomycetales><Esthesia><Eukaryotic Cell><Fever><Generalized Growth><Growth><Heat Shock><Heat shock proteins><Heat-Shock Reaction><Heat-Shock Response><Immune Cell Activation><Immune system><Intracellular Communication and Signaling><Link><Messenger RNA><Methods><Modeling><Molecular><Molecular Chaperones><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Non-Polyadenylated RNA><Physical condensation><Physiologic><Physiological><Process><Proteins><Pyrexia><RNA><RNA Gene Products><Regulation><Ribonucleic Acid><Saccharomycetales><Sensation><Signal Transduction><Signal Transduction Systems><Signaling><Specificity><Stress><Subcellular Process><Temperature><Tissue Growth><Work><Yeast Model System><biologic><biological signal transduction><cell biology><condensation><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><febrile><febris><fungus><immune activation><insight><mRNA><neurodegenerative illness><novel><ontogeny><operation><operations><oxidation><parent award><parent project><proteotoxic><proteotoxicity><response><stress protein><yeast model>