Samrat Mukhopadhyay<\/p>\n\n\n\n
\u200bIndian Institute of Science Education and Research (IISER) Mohali<\/em><\/p>\n\n\n\n Email: mukhopadhyay@iisermohali.ac.in<\/a> Website: https:\/\/www.MukhopadhyayLab.org<\/a> Twitter: @SamratLabMohali<\/a><\/p>\n\n\n\n Cells contain membrane-enclosed organelles that compartmentalize cellular constituents and regulate biochemical processes. A growing body of exciting research now reveals that there is also an alternative mechanism of spatiotemporally-controlled intracellular compartmentalization and organization through biomolecular condensate formation via macromolecular phase separation of proteins and nucleic acids into noncanonical membraneless organelles with emergent material properties. These functional liquid-like biomolecular condensates can undergo aberrant irreversible phase transitions into gel-like or solid-like amyloid aggregates associated with a range of debilitating human diseases [1,2]. Our longstanding interest in prion biology led us to discover that the prion protein (PrP) (well-known for its association with mad cow disease and Creutzfeldt-Jakob disease) can undergo phase separation via weak, multivalent, transient intermolecular interactions between the N-terminal domain. An intriguing disease-associated amber stop codon mutation (Y145Stop) of PrP yields a C-terminally truncated intrinsically disordered fragment. We demonstrated that this fragment spontaneously phase-separates into highly dynamic liquid droplets under physiological conditions [3]. Upon aging, these liquid droplets undergo a liquid-to-solid phase transition into highly ordered, b-rich, amyloid-like aggregates that exhibit a characteristic autocatalytic self-templating behavior. The propensity for the aberrant phase transition is much lower for the full-length PrP indicating an evolutionarily conserved role of the folded C-terminal domain. Our recent results also showed intriguing spatiotemporal modulations in complex coacervation of PrP with other neuronal intrinsically disordered proteins into heterotypic, multi-component, multiphasic, multilayered condensates in the presence of RNA [4,5]. I will also discuss our surface-enhanced Raman scattering (SERS), single-molecule FRET (F\u00f6rster resonance energy transfer), and homoFRET studies that capture exquisite molecular details of in-vitro-reconstituted biomolecular condensates and cellular stress granules derived from neuronal RNA-binding proteins that are associated with Amyotrophic Lateral Sclerosis [6-8].<\/p>\n\n\n\n 1.<\/strong> Mukhopadhyay Nature Chemistry<\/em> (News & Views) (2021) 13, 1028-1030. 2.<\/strong> Dogra et al. J. Am. Chem. Soc.<\/em> (2019) 141, 20380-20389. 3.<\/strong> Agarwal et al. Proc. Natl. Acad. Sci. <\/em>(2021) 118, 45, e2100968118. 4.<\/strong> Agarwal et al. Nature Communications<\/em> (2022) 13, 1154. 5.<\/strong> Rai et al. Proc. Natl. Acad. Sci.<\/em> (2023) 120, e2216338120. 6. <\/strong>Avni et al. Nature Communications<\/em> (2022) 13, 4378. 7.<\/strong> Joshi et al. Nature Communications<\/em> (2023) 14, 7331. 8.<\/strong> Joshi et al. Nature Communications<\/em> (2024).<\/p>\n","protected":false},"template":"","events_category":[15],"class_list":["post-11048","event","type-event","status-publish","hentry","events_category-seminar","entry"],"_links":{"self":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/event\/11048","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/event"}],"about":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/types\/event"}],"wp:attachment":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/media?parent=11048"}],"wp:term":[{"taxonomy":"events_category","embeddable":true,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/events_category?post=11048"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}