PROJECT SUMMARY
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.
