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CATEGORIES:Thesis defense
DESCRIPTION:Title: Transcriptional Reprogramming to Reverse Aging-Associate
 d Transcriptional Dysregulation in Neurons\n\nAbstract:\nIt is unclear what
  the mechanistic contribution of normal aging  is to the neurodegenerative 
 diseases that present in advanced age. This motivates an investigation into
  the molecular characteristics of neuronal aging\, as well as the pursuit o
 f interventions that could reverse neuronal aging or increase neuronal resi
 lience to degenerative mechanisms. We cataloged the molecular differences b
 etween young and old neurons of the mouse brain with single-nucleus paired 
 transcriptional and epigenetic assays\, forming a multi-omic atlas of brain
  aging\, revealing deficits in mitochondrial biogenesis\, proteostasis\, an
 d synaptic gene expression. To reverse these age-associated transcriptional
  profiles\, we targeted endogenous homeostasis-maintenance genetic programs
  by increasing the dosage of relevant Transcription Factors (TFs). We compu
 tationally predicted a library of TFs most likely to engage the target gene
 tic programs by integrating multiple lines of evidence and then produced a 
 library of TFs that we administered in a pool to the aged mouse brain. Our 
 single-nuclear RNA-seq readout describes the transcriptional consequences o
 f each TF perturbation in each cell type in the aged motor cortex. Our resu
 lts highlight certain under-studied TFs with promising rejuvenation potenti
 al and benchmark our algorithmic approaches to predict the effects of TF pe
 rturbations. \n\nThesis Advisor: Myriam Heiman (BCS\, Picower)\n\nThesis De
 fense Committee:\n\nJonathan Weissman\nManolis Kellis\nHongkui Zeng\n\nZoom
  Link: https://mit.zoom.us/j/4565992010?pwd=R1B3MVl2UkdOZzNZOFNSOGpoRFNodz0
 9
DTEND:20250502T190000Z
DTSTAMP:20260310T220214Z
DTSTART:20250502T180000Z
GEO:42.362302;-71.091766
LOCATION:Building 46\, Singleton
SEQUENCE:0
SUMMARY:Alex LeNail Thesis Defense: Transcriptional Reprogramming to Revers
 e Aging-Associated Transcriptional Dysregulation in Neurons
UID:tag:localist.com\,2008:EventInstance_49515583128164
URL:https://calendar.mit.edu/event/alex-lenail-thesis-defense-transcription
 al-reprogramming-to-reverse-aging-associated-transcriptional-dysregulation-
 in-neurons
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