Archives Events
Stefan Taubert, PhD - Department of Medical Genetics, University of British Columbia -- CSB Seminar
CSB Departmental Seminar
Friday, April 10th @ 11:00 am
SPEAKER: Stefan Taubert, PhD - Department of Medical Genetics, University of British Columbia
TITLE: Transcriptional regulation of stress responses in C. elegans and human cancer cells.
ABSTRACT:
The accumulation of molecular and cellular damage is a key driver of aging and age-related diseases such as cancers, type 2 diabetes, and neurodegenerative disorders. Normally, damage accumulation is mitigated by stress response networks. These networks engage evolutionarily conserved transcription factors, which rewire gene expression to promote homeostasis of cells, tissues, and organisms. To identify and study conserved longevity and stress response networks, we use the nematode C. elegans and cancer cell lines. We study a critical and evolutionarily conserved transcription coregulator, the Mediator complex, focusing on Mediator subunit 15 (MED15/MDT-15). Previous work showed that loss of C. elegans mdt-15 or of its key partner, nuclear hormone receptor nhr-49, impairs longevity- and stress-induced gene expression, shortens life span, and sensitizes animals to stressors such as pro-oxidants, hypoxia, or starvation; vice versa, mdt-15 or nhr-49 gain of function increases life span and stress resistance. Downstream, MDT-15 and NHR-49 regulate fatty acid metabolism, autophagy, and other processes to promote longevity and resilience. However, how gene programs are tailor made to each stress and how MDT-15 and/or NHR-49 are activated in longevity or stress contexts remains unclear. To study these problems, we are performing genetic screens for new pathway components and proteomic analysis of NHR-49 using IP-MS and BioID protein proximity labelling in various conditions. Collectively, our studies suggest emerging roles for several kinases and for post-transcriptional mRNA processing and export in MDT-15–NHR-49 stress resilience. Finally, to test if this regulatory network has evolutionarily conserved roles in stress resilience, we deleted MED15 in human A549 lung cancer cells. Transcriptome and functional analysis suggest that MED15 promotes antioxidant and pro-inflammatory signalling, with critical roles in regulating chemokine/cytokine-dependent interactions of cancer cells with immune cells. Collectively, our studies suggest that MED15 and its associated transcription factors control stress resilience across species and that these circuits are critical in the context of at least one age-associated diseases, cancer.
HOST: Arneet Saltzman
LOCATION: Cell and Systems Biology, 25 Harbord Street, Suite 432
LIVESTREAM LINK: https://csb.utoronto.ca/live-stream/
Danesh Moazed, PhD - Department of Cell Biology, Harvard Medical School -- CSB Seminar
CSB Departmental Seminar
Friday, April 17th @ 11:00 am
SPEAKER: Danesh Moazed, PhD - Department of Cell Biology, Harvard Medical School
TITLE: Heterochromatin and Epigenetic Inheritance Mechanisms
ABSTRACT:
The formation of heterochromatin and its faithful inheritance during development and adult life are required for silencing of transposons and lineage-specific cell identity genes. We have developed reporter-based systems that allow us to study the requirements for the establishment of epigenetic maintenance of heterochromatin in fission yeast and mammalian cells. Our work reveals roles for pathways ranging from DNA binding proteins and noncoding RNAs, which mediate specific assembly events, to complexes that mediate the spreading and epigenetic inheritance of heterochromatin. I will discuss our recent results on the roles of specificity factors, RNA decay complexes, and the DNA replication machinery in heterochromatin establishment and maintenance.
HOST: Student invitee - Saltzman Lab
LOCATION: Cell and Systems Biology, 25 Harbord Street, Suite 432
LIVESTREAM LINK: https://csb.utoronto.ca/live-stream/
Eric Lai, PhD - Developmental Biology Program, Memorial Sloan Kettering Cancer Center -- CSB Seminar
CSB Departmental Seminar
Friday, April 24th @ 11:00 am
SPEAKER: Eric Lai, PhD - Developmental Biology Program, Memorial Sloan Kettering Cancer Center
TITLE: Genomes in conflict: The biology of endogenous RNA interference and meiotic drive
ABSTRACT: Selfish meiotic drive systems (SMDs) can distort progeny sex-ratio (SR) and/or induce sterility. If left unchecked, the activity of SMDs can collapse the population, and potentially cause extinction. Although widespread in nature, the molecular mechanisms of SMDs, and how they are silenced to restore Mendelian segregation, remain largely mysterious. Importantly, their rapid evolution means that classic model organisms may not be suited to reveal their fundamental features, breadth and impact. Instead, we used non-model Drosophila species to uncover critical roles for endogenous RNA interference (RNAi), via hpRNA class endo-siRNAs, to suppress incipient sex chromosome conflicts. Genetic studies reveal that these involve de novo meiotic drive loci encoded by the X chromosome. Furthermore, long read genomic data from wild fly lines reveals extraordinary polymorphism and copy number variation in these genes across individuals. We interpret this to reflect an ongoing arms race between SMD distortion and suppression by small RNAs. Beyond hpRNAs, we find evidence for a broader set of endogenous siRNAs produced from diverse types of double stranded RNA, and show that these are also fast-evolving and have regulatory impacts. Overall, our studies highlight the genetic and molecular importance of RNA silencing during recent or active speciation.
HOST: Co-host with CSDB, CSB Trainee host: Una McNally - Harris lab
LOCATION: Cell and Systems Biology, 25 Harbord Street, Suite 432
LIVESTREAM LINK: https://csb.utoronto.ca/live-stream/