Tag: Cori Cahoon

Meiotic recombination is regulated by dosage of synaptonemal complex proteins

Presenter: Amelia Dayton — Biology

Faculty Mentor(s): Cori Cahoon, Diana Libuda

Session: (In-Person) Oral Panel—Daily Dose of Proteins

Meiosis is a specialized cell division that produces haploid gametes, such as sperm and eggs. To ensure each parental genome is inherited properly, cells must pair homologous chromosomes, induce DNA double-strand breaks, repair these breaks as crossovers, and segregate the chromosomes. The synaptonemal complex (SC), a large protein structure, assembles between homologs and facilitates crossing over, which ensures accurate chromosome segregation. Using Caenorhabditis elegans, previous work in the Libuda lab showed that two SC proteins, SYP-2 and SYP-3, have dosage-dependent functions in regulating crossing over. SYP-2 dosage is critical for regulating early crossover steps, while SYP-3 dosage influences the timing of crossover establishment. Crossovers are nonrandomly positioned on chromosomes, and whether SYP dosage influences crossover position remains unclear. To this end, I am using single nucleotide polymorphisms to characterize the positions and rates of crossovers in cells with altered SYP-2 and SYP-3 dosages. Preliminary data on Chromosome X shows that SYP-dosage is crucial for proper crossover positioning. Since the sex chromosomes often behave differently from autosomes, I am also determining the effect of SYP- dosage on crossovers across Chromosome II to establish whether autosomes show similar changes in crossover positioning. Overall, these experiments will define the dosage-dependent manner that SYP-2 and SYP-3 regulate recombination to promote fertility.

Investigating the relationship between heat-stress induced DNA damage and the synaptonemal complex in spermatogenesis

Presenter(s): Cailan Feingold

Faculty Mentor(s): Diana E Libuda & Cori C. Cahoon

Poster 63

Session: Sciences

Male fertility defects affect approximately one-third of couples who are unable to conceive, however many of the male-specific mechanisms that contribute to infertility are unknown. Spermatogenesis, unlike oogenesis and other developmental processes, is sensitive to temperature changes and requires a narrow isotherm of 2-7°C below core body temperature. Exposing spermatogenesis to elevated temperature conditions, both physiological and environmental, have been linked to increased risks of testicular cancer and male infertility. Despite these defects, the mechanisms behind heat-induced male infertility are unknown. In Caenorhabditis elegans, heat stress causes sperm-specific increases in DNA damage and destabilization of the chromosome structures essential for meiotic chromosome segregation. Notably, the largest increase in heat-stress induced DNA damage occurs during late prophase I, which coincides with the stage when the chromosome structures are prematurely lost. Therefore, the proteins involved in establishing these chromosome structures might play a direct role in preventing and/or limiting heat-induced DNA damage. However, the relationship between heat-induced DNA damage and chromosome structures has only been examined using static fixed images, which fail to demonstrate the progression of DNA damage and chromosome structure breakdown relative to one another. To understand the dynamic relationship between heat-induced DNA damage and chromosome structures, fluorescently tagged versions of a DNA damage protein (RAD-51) and a structural protein (SYP-3) will be made and live imaged in whole animals undergoing spermatogenesis both with and without heat stress. Overall, these experiments will determine whether chromosome structure instability directly impacts genome integrity during heat stress in developing spermatocytes.

Development of a new live imaging technique to uncover the mechanisms of heat- induced male infertility

Presenter(s): Cailan Feingold—Biology

Faculty Mentor(s): Diana Libuda, Cori Cahoon

Session 3: The Substance of Us

Male infertility affects approximately one-third of couples who are unable to conceive . Exposing mammalian spermatogenesis to elevated temperatures causes 40% of primary male infertility cases; however, the mechanisms behind this heat-induced male-specific infertility are largely unknown . Similar to mammals, Caenorhabditis elegans also display heat-induced sperm-specific infertility . Following heat-stress, C . elegans spermatocytes have increases in DNA damage that correlate with a premature loss of chromosome structures essential for meiotic chromosome segregation . Using live imaging, I will examine the dynamic relationship between this heat-induced DNA-damage and disassembly of meiotic chromosome structures in spermatocytes . To circumvent immobilization issues with existing current live imaging techniques, I am developing and implementing a new conditional, immobilization method for live imaging fluorescently tagged proteins in both sexes of intact worms . This novel method utilizes the auxin-inducible degron system, which targets degradation of degron tagged proteins in the presence of auxin, and thus can be used to specifically degrade genes that cause severe paralysis . Based on the gene location and predicted function, I selected three genes to degron tag (unc-104, unc-52, unc-18) . Using fertility assays, I confirmed that loss of these three gene products does not interfere with meiosis or fertility . Overall, this novel live imaging system will allow for conditional paralysis of living worms during live imaging experiments, enabling us to examine the dynamics of the heat-induced defects during spermatogenesis .