Faculty
Thomas L Casavant Ph.D.
My research is divided among two areas: 1. High-Performance Parallel and Distributed Computing; and 2. Gene Discovery, Mapping, and Disease Linkage. Since 1986, my work in High-Performance Parallel and Distributed Computing has involved the theory, design, and prototyping of computer systems to solve the largest and most computationally demanding problems. This work involves the design of hardware, software, and the networking/communications to interconnect them. The two patents I hold are for the design of a parallel computing systems, and languages, that allow large numbers of microprocessors to be interconnected to cooperate in the solution of large, complex, computational problems. Since late 1994, I have been involved in the application of these high-performance computing technologies to the specific problem domain of the Human Genome Project. My efforts, in collaboration of members of the College of Medicine, have involved the design of networked systems of computers to analyze large amounts of genetic sequence data taken from mixed tissue libraries of variably expressed mRNA transcripts. Further, processing of this data has required extensive computation to construct genetically anchored maps showing relative locations of all genes. Finally, we have constructed web-based tools to collect, organize, and analyze genetic marker data, pedigree and clinical data to identify linkage between gene candidates and specific diseases including hypertension, obesity, glaucoma, and autism.
Chi-Lien Cheng Ph.D.
My laboratory studies the molecular mechanisms by which environmental signals are incorporated into the growth and developmental program of plants. We concentrate on two aspects, greening and senescence of the leaves. Greening occurs at the beginning of leaf development and senescence precedes the death of a leaf. Both greening and senescence are regulated by internal factors, such as hormones and sugar levels, as well as by environmental factors, such as light. We use a combination of classical genetics, molecular cloning technologies, and biochemistry to identify genes regulating these developmental processes. The overriding strategy in these studies is to isolate mutants defective in these processes, and use these mutants as inroads to understand the developmental programs leading to greening and senescence. Arabidopsis thaliana is our model organism. Arabidopsis is well suited for genetic analysis. The genetic and physical maps of the Arabidopsis genome are well integrated and its sequence is completed. This facilitates cloning the gene of interest. Once the genes are cloned, we can employ molecular technologies to examine the regulation of the gene\'s expression, the biochemical function of the protein it encodes, and the developmental and physiological roles of the protein. The characterization of mutants in greening and senescence is described briefly below. We have identified mutants defective in greening. One of these, cr88, has been characterized and the affected gene cloned. The CR88 gene encodes for a chloroplast-targeted HSP90 molecular chaperone. We are using biochemistry to identify cochaperones that interact with CR88 and genetics to identify the client proteins that require the CR88 chaperone function to mature. To study the senescence process, we isolated mutants that are delayed in this process. One such mutant, sds1, has been characterized. The sds1 mutant exhibits delays in both natural and artificially induced senescence (see figure). In addition, the mutant is less sensitive to sugar levels. The delays in visible phenotypes correlate with delays in the down-regulation of photosynthetic gene expression and in the up-regulation of senescence marker gene expression. We have mapped the SDS1 locus to the North arm of chromosome 1 and are in the process of cloning the gene. The identity of the SDS1 protein will provide vauable information about the interplay of sugar sensing and senescence. The combination of genetic, molecular biological, and biochemical studies will allow us to understand certain aspects of the greening process and the control of senescence during plant development.
Josep M Comeron Ph.D.
We apply a multidisciplinary approach-combining empirical work to obtain sequence data, large-scale genomic analyses, and the development of theoretical, analytical and computational tools-to investigate: 1) variation in the efficacy of natural selection among species and across genomes, 2) the evolution of recombination across genomes and among species, 3) the evolution of introns (presence and size) and genome structure in eukaryotes, 4) the evolutionary consequences of changes in population size, and 5) the genetic basis of speciation. Likely, many mutations important to evolution have much smaller selection coefficients than it is practicable to demonstrate in the laboratory. Population genetics and molecular evolution analyses-the study of nucleotide variability within and between species, respectively-are powerful tools that allow us to detect the action of selection on naturally-occurring mutations, even if the fitness effects of these mutations are extremely weak. We study the causes and consequences of changes in recombination rates among species and across genomes, focusing on the influence of meiotic recombination on the efficacy of selection in eukaryotes. To measure possible changes in the effectiveness of selection, we study weakly selected mutations such as synonymous mutations (changes in the coding sequence that do not alter protein sequence) and small insertion/deletions (indels). The same population genetics techniques that are commonly applied to nucleotide changes can be also applied to genomic features, allowing us to investigate the forces involved in the evolution of gene number, the origin of introns, the evolution of exon-intron structures, and ultimately genome size. This genomics-meets-population genetics approach (i.e., population genomics) can be implemented with computer simulations mimicking the evolutionary process (in silico evolution), a computationally-intensive technique that provides new and valuable insights into the expected outcome of complex evolutionary processes. We also apply molecular evolution and population genetics techniques to study recent speciation events. In particular, we investigate Drosophila species to gain insight into the evolutionary patterns of genes involved in phenotypic differentiation and reproductive isolation.
Robert A Cornell Ph.D.
The neural crest, a transient population of multi-potent precursor cells exclusively found in vertebrate embryos, gives rise to neurons, glia, and melanocytes, among other cell types. The neural crest is thus an attractive model in which to explore universal cellular developmental events like fate specification, migration, survival, and differentiation. Moreover, when these events go wrong in neural crest there can be dire consequences for the individual, including cleft lip and palate, neuroblastoma, neurofibromotosis, and melanoma. We strive to identify the gene products that regulate developmental decisions within the neural crest. Better knowledge of these genes will improve the ability of clinicians to predict the likelihood of an individual to succumb to such diseases. Moreover, developmental regulatory genes represent potential therapeutic entry points for a wide range of diseases. We use forward and reverse genetics methods in zebrafish towards this end. http://www.anatomy.uiowa.edu/pages/directory/faculty/cornell.asp
