Our studies of nematode reproduction focus on the signaling processes between sperm cells and their environment. Understanding how to manipulate this process may be useful in preventing or limiting the spread of infection by parasitic nematodes, which are a world-wide health problem. Additionally, our studies of one class of molecules involved in sperm differentiation, protease inhibitors, may yield direct insights into human disease, since alterations in regulatory proteolysis are implicated in numerous diseases.
We are studying the functional cell biology of sperm. Cues from outside sperm cells signal them to complete their differentiation process and guide their subsequent migration towards the egg. We are working to identify the signaling molecules that trigger these cellular behaviors and to determine how these signals are transduced into changes in cell shape and the direction of migration.
To analyze these processes, we are using the nematode Caenorhabditis elegans, which offers many advantages for studying reproductive cell signaling. C. elegans exists as two sexes: males and self-fertilizing hermaphrodites, both of which make sperm. Nematode sperm are amoeboid and move by crawling; however, like sperm with flagella, they must undergo an elaborate process of spermiogenesis (termed activation) to transform round haploid spermatids into highly differentiated, polarized spermatozoa capable of motility and fertilization. This process occurs extremely rapidly and involves no new gene expression.
We seek to understand the sex-specific and spatiotemporal signals that regulate the cellular reorganization that occurs during sperm activation. We have identified a serine protease inhibitor that functions to prevent premature sperm activation from occurring within males and is required for male fertility. We are using a variety of genetic and molecular approaches to understand how proteases regulate sperm activation and to identify other molecules involved in triggering this process.
We are also interested in how sperm cells compete with one another to fertilize eggs. If male sperm are available within the C. elegans hermaphrodite reproductive tract, they are used preferentially. Previous experiments designed to test specific models of competition indicated that male precedence appears to be due to a sperm-intrinsic factor(s) and correlates with the larger size of male sperm. However, the molecular basis of this phenomenon is not understood. We are using genetic screens to identify factors important for male precedence. This strategy should yield insights into general mechanisms of the cellular interactions between sperm and the female reproductive tract, egg, and other sperm.
References to Publications:
Fenker KE, Hansen AA, Chong CA, Jud MC, Duffy BA, Norton JP, Hansen JM, Stanfield GM. (2014). SLC6 family transporter SNF-10 is required for protease-mediated activation of sperm motility in C. elegans. Dev Biol, 93(1):171-82.
Ellis RE, Stanfield GM. (2014). The regulation of spermatogenesis and sperm function in nematodes. [Review] Semin Cell Dev Biol, 29:17-30.
Smith JR, Stanfield GM. (2012). A seminal fluid protease activates sperm motility in C. elegans males. [Commentary] Worm, 1(3), 151-4.
Smith JR, Stanfield GM. (2011). TRY-5 Is a Sperm-Activating Protease in Caenorhabditis elegans Seminal Fluid. PLoS Genet, 7(11), e1002375.
Stanfield GM, Villeneuve AM. (2006). Regulation of Sperm Activation by SWM-1 Is Required for Reproductive Success of C. elegans Males. Curr Biol, 16(3), 252-63.
Colaiacovo MP, Stanfield GM, Reddy KC, Reinke V, Kim SK, Villeneuve AM. (2002). A targeted RNAi screen for genes involved in chromosome morphogenesis and nuclear organization in the Caenorhabditis elegans germ line. Genetics, 162(1), 113-28.
Kelly KO, Dernburg AF, Stanfield GM, Villeneuve AM. (2000). Caenorhabditis elegans msh-5 is required for both normal and radiation-induced meiotic crossing over but not for completion of meiosis. Genetics, 156(2), 617-30.
Stanfield GM, Horvitz HR. (2000). The ced-8 gene controls the timing of programmed cell deaths in C. elegans. Mol Cell, 5(3), 423-33.
Wu YC, Stanfield GM, Horvitz HR. (2000). NUC-1, a Caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis. Genes Dev, 14(5), 536-48.
Metzstein MM, Stanfield GM, Horvitz HR. (1998). Genetics of programmed cell death in C. elegans: past, present and future. [Review] Trends Genet, 14(10), 410-6.
Gillian Stanfield, Ph.D.
Department of Human Genetics
University of Utah
15 N 2030 E rm. 6110B
Salt Lake City, Utah 84112-5330