# A MAP Kinase that controls the post-meiotic phase of the yeast life cycle.

> **NIH NIH F33** · THOMAS JEFFERSON UNIVERSITY · 2020 · $11,259

## Abstract

Project Summary/Abstract: Meiosis is the specialized form of cell division that generates haploid gametes
from diploid precursors. It is essential for the life-cycles of almost all eukaryotic organisms. Understanding
meiotic regulatory mechanisms is relevant to human health since defects in meiosis cause infertility, cancer,
and birth defects. Baker's yeast is an outstanding model system to study meiotic development. In response to
starvation, diploid cells enter meiotic development and generate four haploid cells within the mother cell. Early
events include meiotic DNA replication, homolog pairing, and genetic recombination. After the completion of
genetic recombination, cells undergo 2 rounds of chromosome segregation without an intervening S-phase.
After the second meiotic division (MII), the haploid products are encased in spore walls that protect the
haploids from environmental insults. Although yeast has taught us much about meiotic S-phase, prophase, and
the meiotic divisions, much less is known about the processes that occur after MII has taken place. One
reason we know so little about the post-meiotic phase of this program is that the spore walls are experimentally
impenetrable; extracting macromolecules under native conditions or monitoring molecules using
immunofluorescence methods has until recently been nearly impossible. Previous work in the sponsor's
laboratory has identified a meiosis-specific MAPK named Smk1 that controls the post-meiotic program of spore
formation. This led to the discovery that Smk1 activates the expression of late meiosis-specific genes, which
are uniquely expressed after the spore wall has assembled. This proposal takes advantage of engineered
yeast strains that produce permeable spore walls so that the intracellular and nuclear events that occur during
the late stages of meiotic development can be studied. The proposal also takes advantage of engineered
forms of Smk1 that are sensitive to cell-permeable purine analogs (smk1-as) that can be used to turn Smk1 on
and off. Mutations that permeabilize the spore wall with smk1-as are combined in a genetic background that
undergoes meiosis in a highly synchronous manner, and this will be used to define the complete set of late
meiosis-specific genes that are regulated by Smk1 (aim 1). We will also test the hypothesis that Smk1 is
recruited to late meiosis-specific transcriptional promoters (aim 2). Preliminary data suggests that Smk1
phosphorylates the C terminal domain of RNA polymerase, and we will also test this hypothesis and whether
these modifications take place at late meiosis specific genes as they are being transcribed (aim 3). Studies of
how meiotic events are regulated in yeast may provide insights into human gametogenesis, which have clinical
implications in solving infertility, miscarriages, and developmental disorders. The principal investigator (Julia
Lee-Soety) intends to conduct this work during her sabbatical leave in Dr. Edward Winter's laborator...

## Key facts

- **NIH application ID:** 10005813
- **Project number:** 5F33GM134600-02
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** JULIA Y LEE-SOETY
- **Activity code:** F33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $11,259
- **Award type:** 5
- **Project period:** 2019-09-01 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005813

## Citation

> US National Institutes of Health, RePORTER application 10005813, A MAP Kinase that controls the post-meiotic phase of the yeast life cycle. (5F33GM134600-02). Retrieved via MORVS 2026-10-27 from https://api.morvs.ai/grant/nih/10005813. Licensed CC0.

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