Faculty & Staff
Samuel M. Politz
Associate Professor
Faculty Listing
Office: Life Sciences and Bioengineering Center, 4023
Phone: +1-508-831-5028
Fax: +1-508-831-5936
spolitz@wpi.edu
Educational Background
- B.S., Louisiana State University at Baton Rouge, 1973
- Ph.D., University of California at Los Angeles, 1978
- Postdoct, University of California at Santa Cruz, 1982
- Postdoct, University of California at Santa Cruz, 1984
Research & Teaching Interests
Genetic and immunological aspects of development of the nematode Caenorhabditis elegans
Research
Surface Antigen Switching in Nematodes:
Our laboratory studies the genetic control of surface composition in the nematode Caenorhabditis elegans. We are interested in this feature of postembryonic development because of its adaptive significance in nematode parasitism. Parasitic nematodes infect about one quarter of the human population and therefore pose a serious public health problem, particularly in undeveloped countries. The potential importance of genetic control of surface composition to parasitism is suggested by Trichinella spiralis infections of mammals. Stages of the parasite appearing late in infection express different surface molecules and escape the host immune attack directed against the stages present earlier in infection.
C. elegans is a popular organism for studying the genetic control of development. It has been subjected to thorough cellular and genetic analysis, including an international project currently underway to determine the DNA sequence of its entire genome. Although it is a free-living soil species, C. elegans shares many developmental and anatomical features in common with parasitic nematodes, suggesting that underlying mechanisms controlling surface molecule expression may be similar. The extensive database and methodology available for working with C. elegans make it the model organism of choice for studying the mechanisms of surface molecule expression in nematodes.
All nematodes have five post-embryonic stages (L1 through L4 and adult) separated by four molts. At each molt a new multi-layered cuticle composed primarily of collagen, is synthesized. Outside of this multi-layered extracellular matrix is a 5-20 nm thick surface coat composed primarily of glycoproteins. A surface protein of the parasite Toxocara canis, identified by Maizels and co-workers, and a C. elegans surface protein, identified by us, share properties with vertebrate mucins that line, lubricate, and protect epithelial cell layers. Like the vertebrate mucins, but unlike proteins of the other cuticle layers, surface coat molecules are readily shed from the surface into the environment.
Surface composition can change at the molts, when a new cuticle is made, so that stage-specific surface differences occur. Surface composition can also change within a single developmental stage, e.g., in response to a new host or host tissue. We use the term surface antigen switching to mean any mechanism that results in the restriction of particular surface molecules to a specific developmental time or stage. Despite its potential significance, the genetic control of surface antigen expression is poorly understood, and therefore is the primary experimental focus in our laboratory.
We have used genetic analysis to identify genes that are involved in specifying surface composition in C. elegans. Our method has been to develop fluorescently tagged antibody probes that recognize surface molecules on live worms, and use these to screen for mutants with altered patterns of surface expression. Our antibody probes bind to the surface of live worms without fixation or other modification. This allows us to pick individual mutants directly under the fluorescent microscope and establish mutant stocks readily.
We have identified two type of mutant phenotypes, which we refer to as Srf phenotypes. First, some mutant phenotypes appear to be defective in surface molecule biosynthesis, and this lesion unmasks molecular features that are normally hidden. These are called Srf defective phenotypes. We believe that the genes identified encode either the surface molecules themselves or enzymes involved in their processing (e.g., glycosyltransferases that put sugars on the surface proteins). We are currently attempting to clone two of these defective genes, srf-2 and srf-3., in order to begin to understand the pathways of biosynthesis of nematode surface proteins.
Second, and perhaps most interesting, are mutant phenotypes that alter timing of expression of a stage-specific surface marker recognized by a monoclonal antibody probe on the wild-type L1 stage. The mutants express this surface marker at all larval stages, L1 through L4. This phenotype suggests that the gene functions as a genetic switch to turn off expression of the antigen after the L1 stage. The mutations that result in this phenotype fall into two classes. One class defines the new gene srf-6. The other mutations are in previously identified genes involved in transducing environmental signals that modulate formation of the C. elegans dauer larva. The dauer larva is a developmentally arrested dispersal stage that arises as an alternative to the L3 when stressful environmental conditions are sensed. We investigated this relationship in collaboration with Don Riddle's laboratory at the University of Missouri, and found that although some genes affect both dauer formation and surface antigen switching, the two processes are controlled differently.
Some of the dauer formation genes encode growth factor receptors similar to those used by vertebrate animals. This supports the idea that intercellular signalling responses also control surface antigen switching. We also have shown that the L1 antigen's expression can be induced at a later larval stage in the wild-type, by growing the worms under specific environmental conditions. We are currently investigating both the nature of the inducing chemical signal, as well as the mechanism by which the worms detect it. Understanding this would not only help explain responses of nematodes to external conditions, but might allow formulation of a means to interfere with the ability of parasitic nematodes to make surface changes.
Finally, the srf-6 gene, which we hypothesize is involved in surface antigen switching, is being subjected to molecular analysis. The gene fortuitously is located in a chromosomal region that has been completely cloned and analyzed by the genome sequencing project. By injecting wild-type DNA fragments into the gonad of a srf-6 mutant and looking for correction of the phenotype in the offspring (a procedure referred to as marker rescue), we have identified a 30,000 base pair fragment that contains the functional srf-6 gene. Further narrowing of this region to a single-gene sized fragment, and determination of the DNA sequence alteration in srf-6 mutants, should allow us to determine what the gene encodes and begin to understand how it controls surface antigen switching.
Recent Publications
Years of Service at WPI
- 1988-1994, Assistant Professor
- 1994-Present, Associate Professor