Talks

Ataxin-2 is a translational control molecule mutated in spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS). While intrinsically disordered domains (IDRs) of Ataxin-2 (Atx2) facilitate mRNP condensation into granules, how IDRs work with structured domains to enable positive and negative regulation of target mRNAs remains unclear. Using TRIBE (Targets of RNA-Binding Proteins Identified by Editing) technology, we identified an extensive dataset of Atx2-target mRNAs in the Drosophila brain. Ataxin-2 interactions with AU-rich elements in 3’UTRs modulate stability/ turnover of a large fraction of these target mRNAs. Further genomic and cell biological analyses of Atx2 domain-deletions demonstrate that Atx2: (a) interacts closely with target mRNAs within mRNP granules; (b) contains distinct protein domains that drive or oppose RNP-granule assembly; and (c) has additional essential roles outside of mRNP granules. These findings increase understanding of neuronal translational control mechanisms and inform strategies for Ataxin-2-based interventions under development for neurodegenerative disease.

**Title:** The Next Frontiers of Particle Physics: Linking Theory, Experiment, and Other Disciplines **Abstract:** Particle physics stands at a pivotal moment. While high-energy colliders have long been the primary tool for discovery, new ideas and technologies are opening complementary paths. In this talk, I will survey some of the most pressing open questions in particle physics, including the nature of dark matter and the possible existence of axions. I will highlight recent developments that bridge theory with experiment, such as the DarkQuest beam-dump experiment at Fermilab (that I started developing as a postdoc at Perimeter), novel dark matter detection strategies using condensed matter systems, and the potential of quantum sensing and gravitational wave observatories to probe dark sectors. This interdisciplinary perspective reflects a broader shift in the field: breakthroughs are increasingly likely to emerge from the interplay of particle physics with other disciplines. I will also reflect on my own journey, from a postdoc at Perimeter Institute to a professor leading a research group at the University of California, Santa Cruz, emphasizing how creativity, cross-field connections, community engagement, and mentoring are shaping the next frontiers of discovery.