Temperature-sensitive germline structures and temperature thresholds of fertility in caenorhabditis nematodes

This federal Project Grant award from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), provides $458,050.00 to Marquette University to conduct research on the temperature-sensitive structures and processes that underlie fertility in nematode species.

The key objectives of this 3-year project are to: 1) Determine how the stability of the synaptonemal complex, a critical meiotic structure, contributes to the thermal limits of fertility, and 2) Assess how the stability of P granules, nematode-specific germ granules, impacts the temperature thresholds for fertility loss. This comparative research across Caenorhabditis nematode species aims to elucidate the conserved, temperature-sensitive mechanisms in germ cells that lead to reduced fertility in numerous species, including humans, when exposed to elevated temperatures.

Abstract

Species from worms to humans show a critical loss of fertility when exposed to elevated temperatures. This conserved response to temperature stress affects both males and females. Interestingly while every species tested, including humans, appear to have a thermal limit of fertility below temperatures that lead to death, even closely related species can have different thermal limits of fertility. What then could be the germline specific structure/pathway that experiences a conserved temperature sensitive failure, but that the specific temperature when IT fails can be modified? Two possible such structures that are germline specific are the synaptonemal complex (SC) and germ granules. Both structures are necessary for fertility and exhibit liquid-like properties that make them inherently structurally temperature sensitive. Notably, proteins within these structures contain intrinsically disordered domains that contribute to the liquid-like properties of the structures and are also rapidly evolving. In the model nematode c. Elegans, both structures have been shown to have structural failure around or just above the temperature where c. Elegans goes sterile. Using a comparative model of caenorhabditis nematodes that have different thermal limits of fertility, we will test if the SC and p granules (nematode specific germ granules) are the critical structures that fail during high temperature stress. In this grant we will test the hypothesis that the liquid-like physical properties of the synaptonemal complex and p granules predisposes them to failure during temperature stress leading to loss of fertility at elevated temperatures using two aims. In aim 1 we will determine how synaptonemal complex stability plays a role in the thermal limit of fertility. These experiments will specifically add to our understanding how conserved is the temperature sensitivity of meiotic processes. In aim 2 we will determine how p granule stability plays a role in the set point of the thermal limit of fertility. These experiments will add to our understanding of how germ granules are vulnerable to temperature stress. This work will elucidate why germ cells across species are so sensitive to increased temperature and help explain why species, including humans, are losing fertility in the face of climate associate higher temperatures.