Title: Assistant Professor
Area of Study: Developmental Genetics and Evolution
Phone: (252) 737-4257
Fax: (252) 328-4718
Office: Howell Science N407A
Address: Department of Biology
East Carolina University
Greenville, NC 27858
1. The evolution of morphological novelties: studying change in organ shape.
* How new body morphologies arise remains an unresolved problem though it has been studied extensively by such renown’s as Jean-Baptist Lamarck and Charles Darwin since the early 1800s. It is an important question as new morphologies allow the colonization of different ecological niches and the adoption of new life histories. Why has it been so hard to resolve? First, because answering this problem relies upon integration of ecology, development, and genetics. Second, because even when parts of the body are thought to be analogous, the change occurred in distant time and has been obscured by subsequent evolutionary flotsam, e.g. the evolution of arthropod wings, gills and spinnerets from the same ancestral organ.
* Nematodes are the perfect comparative system to address this question as the system allows evo-devo investigations at the level of species, populations, individuals, cells, pathways and molecules with a tool set for field ecology, forward genetics, reverse genetics, cell biology, biochemistry, and genomics that is almost unprecedented. When combined with the comparative data provided by the model nematode C. elegans, an exemplar for the study of animal development and diseases, it is a truly formidable comparative system. Pristionchus pacificus is related to C. elegans; it is far enough away to have morphological differences but close enough to allow the assignment of homology of organs, tissues, cells, development, and molecules.
* The gonad of P. pacificus has a different shape in comparison to C. elegans and represents a derived trait that resulted from changes in the absolutely conserved metazoan Wnt and Netrin pathways. This research focuses upon investigating the molecular changes in these two pathways using population genetics and phenotypic analysis, observation of cell interactions throughout nematode phylogeny, developmental genetic studies in the laboratory, and biochemical approaches to analyze causative differences in the regulation and action of genetic networks and molecules. This system offers the potential for tremendous strides in data acquisition and analysis of evolutionary developmental processes. Additionally, this work focuses on the evolution of the gonad; an organ that remains enigmatic and poorly understood in many ways, although it is an essential organ and the germ line the only immortal tissue. Lastly, we are studying naturally occurring variations in essential metazoan Wnt and Netrin pathway genes; these alternative alleles represent changes putatively analogous to the types of changes that have led to the evolution of the vertebrate animal-vegetal axis organizer and human disease states.
2. The toxicity of heavy metals, nickel as an environmental contaminant and mutagen.
* Nickel toxicity results in respiratory illnesses, increased rates of cancer, and potentially birth defects (1). As a metal it is innocuous. In compounds it is a toxin that takes two forms, either highly water soluble salts capable of long distance contamination through waterways or highly insoluble compounds difficult to get rid of. Both types of compounds lead to respiratory diseases and are mutagenic. Evidence suggests that the insoluble forms may be more damaging to human health. Nickel’s mode of action is not fully understood, nickel’s mutagenic properties may result in part from the fact that the Ni2+ cation is capable of creating reactive oxygen species, binding to the DNA backbone, and potentially disrupting DNA replication and repair. In North Carolina, nickel is an incidental byproduct of mining in the mountains, manufacturing of any item with metal components such as cars and boats, and human waste sites where manufactured items are deposited. Surprisingly few studies have been conducted in the US on the extent and resulting consequences of nickel toxicity on our citizens.
* We have pioneered a new line of research to develop biological and biotechnological tools to monitor nickel contamination in different sediments and waters. In that work we developed an easy, quick, inexpensive, and potentially commercial laboratory bioassay sensitive to investigating effects of nickel toxicity at the level of individual tissues. In this assay larval nematodes are added to both contaminated and uncontaminated sediments and waters in tissue culture wells, grown for one generation, and assayed for survivorship, growth, and fecundity. We found nickel reduces survivorship, life span, and decreases the number of progeny that makeup the next generation. Importantly nematodes show a dosage effect, most tested invertebrates showed an all or nothing response, making nematodes ideal for monitoring specific levels of nickel contamination. The assay we developed would be of interest to any industry facing environmental impacts from nickel or other heavy metals, e.g. mining, manufacturing, waste management, energy, and agricultural run off.
* We seek to expand this new line of research. In our hands, nickel has already proven to be a potent inducer of apoptosis/programmed cell death and mutagen in our animal model and should give rise to data applicable to human health. Thus, we hypothesize that genome damage is responsible for many of these effects. We will define the strength of nickel as a mutagen, look at the effects of nickel in generating birth defects by damaging DNA in the animal germ line, look at animal response to nickel based upon gene transcription activity, and identify potential gene targets that can be addressed using modern molecular biotechnology approaches to develop drugs and therapies to prevent or treat the results of nickel toxicity.
My laboratory is always looking for students with drive and ambition that are interested in our topics. Prospective PhD/doctoral, MS, and undergraduate students are encouraged to apply to the program and contact me at: firstname.lastname@example.org
Douglas C., Besser J., Ingersoll C.G., and Rudel D. (in preparation) The effects of nickel toxicity upon survival, growth, and reproduction in nematodes. Environment International.
Besser J., William Brumbaugh W., Kemble N., Ivey C., Kunz J., Rudel D., and Ingersoll C.G. (2011) Toxicity of nickel-spiked freshwater sediments to benthic invertebrates: spiking methodology, species sensitivity, and bioavailability. USGS Open-File Report Series.
Rudel, D., Tian, H., and Sommer R.J. (2008). The evolution of a morphological novelty: An essential role for Wnt signaling in P. pacificus gonadal arm extension. Proc Natl Acad Sci USA, 105, 10826-10831.
Rudel, D., Riebesell, M. and Sommer R. J. (2005). Gonadogenesis in Pristionchus pacificus and organ evolution: development, adult morphology and cell-cell interactions in the hermaphrodite gonad. Developmental Biology 277, 200-221.
Rudel, D. and Sommer R. J. (2003). The evolution of developmental mechanisms. Developmental Biology, Developmental Biology 264, 15-37.
BIOL 1100. Principles of Biology.
BIOL 2100, 2101. Basic Laboratory Methods for Biotechnology.
BIOL 3260. Cell and Developmental Biology.
BIOL 6220. Special Topics in Evolution: Evolution and Development.
MS in Ecology and Evolution
The toxic affects of nickel in sediment and water.
MS in Molecular Biology and Biotechnology
Nickel as a mutagen and inducer of apoptosis
MS in Molecular Biology and Biotechnology
Localization of the Netrin receptors and organ shape change.
Kelly A. Mahoney