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My lab aims to define the principles and regulation of meiotic differentiation. This process, also known as gametogenesis, is a conserved developmental program that creates life for the next generation by forming reproductive cells called gametes. Because gametogenesis contains endogenous pathways that prevent age-associated damage from being passed onto progeny, mechanistic dissection of this program offers unique insights into the biology of aging as well as potential therapeutic avenues to combat age-associated diseases including cancer and neurodegeneration. Accordingly, a fundamental question emerges as to how the fitness of gametes is ensured during their production such that they contain the appropriate nuclear and cytoplasmic content to make healthy progeny. Using budding yeast Saccharomyces cerevisiae as a primary model system, we address this question in two complementary frameworks: First, in the context of gene regulation, with the aim of understanding how the essential meiotic processes that ultimately drive cellular rejuvenation are controlled by the meiotic transcriptional program. Second, we study meiotic differentiation in the context of aging, with the aim of understanding how gamete formation promotes cellular rejuvenation and how meiotic cells ensure that age-associated damage such as protein aggregates and dysfunctional organelles are prevented from being transmitted to subsequent progeny. We further extend our studies to multicellular and human cell line systems with an eye on therapeutic potential of our findings.
My lab aims to define the principles and regulation of meiotic differentiation. This process, also known as gametogenesis, is a conserved developmental program that creates life for the next generation by forming reproductive cells called gametes. Because gametogenesis contains endogenous pathways that prevent age-associated damage from being passed onto progeny, mechanistic dissection of this program offers unique insights into the biology of aging as well as potential therapeutic avenues to combat age-associated diseases including cancer and neurodegeneration. Accordingly, a fundamental question emerges as to how the fitness of gametes is ensured during their production such that they contain the appropriate nuclear and cytoplasmic content to make healthy progeny. Using budding yeast Saccharomyces cerevisiae as a primary model system, we address this question in two complementary frameworks: First, in the context of gene regulation, with the aim of understanding how the essential meiotic processes that ultimately drive cellular rejuvenation are controlled by the meiotic transcriptional program. Second, we study meiotic differentiation in the context of aging, with the aim of understanding how gamete formation promotes cellular rejuvenation and how meiotic cells ensure that age-associated damage such as protein aggregates and dysfunctional organelles are prevented from being transmitted to subsequent progeny. We further extend our studies to multicellular and human cell line systems with an eye on therapeutic potential of our findings.
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bioRxiv : the preprint server for biology (2023)
GENETICSno. 2 (2023)
Johanna Kociemba,Andreas Christ Sølvsten Jørgensen, Nika Tadic, Anthony Harris,Theodora Sideri, Wei Yee Chan,Fairouz Ibrahim,Elcin Unal,Mark Skehel,Vahid Shahrezaei, Orlando Arguello-Miranda,Folkert J. van Werven
bioRxiv (Cold Spring Harbor Laboratory) (2023)
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