Functional Genomics & Bioinfomatics
- Center for Animal Functional Genomics
- Chou, Karen (toxicology, animal health, reproduction)
- Cibelli, Jose (cellular reprogramming, nuclear transfer, embryonic stem cells)
- Coussens, Paul (molecular pathogenesis, immunobiology, functional genomics)
- Ernst, Cathy (swine and bovine molecular genetics, growth biology, meat science)
- Ireland, James (endocrinology of reproduction, fertility, functional genomics)
- Smith, George (reproduction, ovarian function, stress physiology, functional genomics)
- Templeman, Robert (biometry, livestock genetic evaluation, functional genomics)
- Weber Nielsen, Miriam (dairy nutrition, endocrinology, mammary physiology)
The Center for Animal Functional Genomics (CAFG) houses equipment and resources for application of functional genomics to problems in livestock, companion animals, and aquatic species. High-throughput laboratory robotics are used to help create genomic resources and cDNA microarrays for species under study. The CAFG is fully equipped to process and image cDNA and oligonucleotide microarrays. Faculty, students, and staff within the Department of Animal Science have the opportunity to work within the CAFG and assist with creation of unique cDNA microarrays or utilize existing resources. To date, the CAFG has prepared microarrays for:
- long oligo bovine = 10K genes
- long oligo porcine = 13K genes
- zebra mussel foot = 700 genes
- rainbow trout = 8K genes
- gene discovery in cattle = 18,263 genes
- study of bovine immunobiology = 1,400 genes
- bovine mammary physiology = 1,200 genes
- canine retinal degeneration = 400 genes
- swine skeletal muscle biology = 1,000 genes
- behavior and brain physiology in swine = 1,000 genes
In addition to microarray capability, the CAFG houses instruments for quantitative real-time RT-PCR. These instruments are available to faculty, staff, and students in the Department of Animal Science as well as other departments on campus. GenePix Pro 6.0 software is available in the center for spot alignment. Acuity software is also in the CAFG to help with microarray analysis.
My laboratory studies the exposure and health effects of environmental chemicals in mammalian species, with a focus on developmental and reproductive toxicity. The laboratory examines the mechanism of toxicity of pesticides and endocrine disruptors on testicular function, sperm and egg production, and fertility. The target mechanisms include the functions of endocrine systems, production of reactive oxygen species, and the relationship between clusters of alternations in gene expression and long-term reproductive performance. A second major focus of my laboratory is the development of improved semen preservation methods for livestock. The study models include laboratory animals, livestock, and cultured gametes.
Our Cellular Reprogramming Laboratory focuses in two aspects of developmental biology. (1) Nuclear Transfer—Cloning: A number of different laboratories, including our own, have demonstrated that a somatic (body) cell, once fused with an egg, is capable of generating not only stem cells (ref 1) but a whole new organism as well (refs 2-4). Interestingly, we still do not comprehend how this is possible. Our laboratory focuses on understanding the molecular events that lead to the transformation of a somatic nucleus into an embryonic-pluripotent one. Insights into the mechanism of de-differentiation will help us generate cloned animals at optimal efficiency for their use in agriculture and medicine (ref 5). (2) Primate Embryonic Stem Cells: Embryonic stem (ES) cells are capable of maintaining an undifferentiated or ‘pluripotent’ state in vitro. At the same time, by modifying the culture conditions, they can generate daughter cells capable of forming all the tissues in the body. We have demonstrated that somatic cells can be turned into ES cells either by nuclear transfer (cloning; ref 1) or by parthenogenesis (ref 6), and that these cells can later be induced to differentiate into multiple complex tissues (ref 6). In order for us to understand how the state of pluripotency is reached and maintained, ES cells are carefully analyzed at the molecular level. Our challenge is now to learn how to produce these cells without having to relay on eggs (ref 7).
Cibelli JB, Stice SL, Golueke PJ, et al. (1998) Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells. Nat Biotechnol 16: 642-646.
Cibelli JB, Stice SL, Golueke PJ, et al. (1998) Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280: 1256-1258.
Lanza RP, Cibelli JB, Blackwell C, et al. (2000) Extension of cell life-span and telomere length in animals cloned from senescent somatic cells [see comments]. Science 288: 665-669.
Lanza RP, Cibelli JB, Faber D, et al. (2001) Cloned cattle can be healthy and normal. Science 294: 1893-1894.
Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP. (2002) The health profile of cloned animals. Nat Biotechnol 20: 13-14.
Cibelli JB, Grant KA, Chapman KB, et al. (2002) Parthenogenetic stem cells in nonhuman primates. Science 295: 819.
Cibelli J, Kiessling A, Cunniff K, Richards C, Lanza R, West M. (2001) Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development. e-biomed: The Journal of Regenerative Medicine Volume 2.
Paul M. Coussens, Professor
Principal Investigator, Molecular Pathogenesis Laboratory
Depts. Animal Science and Microbiology and Molecular Genetics
Chris Colvin, Research Technician and Laboratory Coordinator
The Molecular Pathogenesis Laboratory (MPL) focuses on the nature, cause, and host response to infectious diseases in livestock species. As many of the pathogens of importance to livestock species are zoonotics, our work often has biomedical implications, as well as relevance to animal health. Pathogens currently under study with a network of national and international collaborators include Mycobacterium paratuberculosis (Johne’s disease), M. bovis (bovine tuberculosis), bovine viral diarrhea virus, Brucella abortus, and several parasitic diseases in cattle. Work within the MPL is aided by an outstanding base of state-of-the-art equipment and tools for functional genomics. Although highly molecular in our approach to studying pathogenesis, all students in the MPL work with the appropriate host species, gaining experience in sampling and recognizing the effects of infectious disease. Students within the MPL also have ample opportunities for travel to multiple international laboratories of our collaborators during their course of study.
Catherine W. Ernst, Professor
Principal Investigator, Molecular Genetics Laboratory
Nancy Raney, Research Technician and Laboratory Coordinator
The overall goal of the Molecular Genetics Laboratory is to identify and evaluate molecular markers and genes for the genetic improvement of pigs and beef cattle with emphasis on performance traits, carcass composition and meat quality. Current projects include a genetical genomics project in pigs that involves integration of genetic marker and gene expression data for identifying genes controlling skeletal muscle and fat deposition and their relationship to growth, carcass merit and meat quality traits. Additional projects include identification of differentially expressed genes in developing pig skeletal muscle, transcriptional profiling of pigs infected with PRRS virus, and evaluation of behavior and temperament traits and their association with production traits in beef cattle and pigs. These projects are in collaboration with Drs. Juan Steibel, Ron Bates and Joan Lunney (USDA-ARS BARC, leader of the PRRS Host Genetics Consortium), as well as other colleagues at MSU, throughout the US, and in Brazil, Thailand, Korea and China.
James J. Ireland. Professor
Director, Molecular Reproductive Endocrinology Laboratory
Depts. Animal Science and Physiology
Janet L.H. Ireland, Laboratory Coordinator
Fermin Jimenez-Krassel, Chief Research Associate
Our laboratory focuses on elucidation of the physiological role hormones, growth factors and cytokines have in regulation of selection, growth, and function of dominant follicles in cattle; and on use of molecular technology (DNA array, real-time PCR) to identify new genes potentially involved in aging-induced alterations in selection, growth, differentiation and function of dominant follicles. We are keenly interested in identification of the intrafollicular factors that regulate aromatase activity in granulosa cells of dominant follicles because of the pivotal physiological role estradiol has in reproduction and other non-reproductive processes. From a practical standpoint, we are interested in development of new diagnostic methods to identify cattle with superior fertility. Our laboratory has considerable expertise in large animal surgery (including utero-ovarian vein cannulations for blood sampling and ovariectomy), ultrasound analysis of follicular development, ultrasound-guided needle biopsy of ovarian follicles, ultrasound-guided intrafollicular injection of drugs, ELISA, RIA, Northern and immunoblot analysis, DNA array, PCR, protein purification, antibody development, and cell culture.
Research efforts in the Molecular Animal Reproduction and Neuroendocrinology Laboratory have focused on investigation of fundamental mechanisms that regulate ovarian function in farm animals and the physiological and neuroendocrine mechanisms involved in regulation of the stress response. We have obtained new insight into the hormonal regulation and regulatory role of members of the matrix metalloproteinase gene family in control of follicle rupture and the hormonal regulation and physiological role of various components of the corticotropin releasing factor (CRF) system in promoting the stress response. Recent research efforts also utilize functional genomics approaches to identify specific components of the oocyte transcriptome [catalog of genes expressed in the female germ cell] that play a key role in regulation of folliculogenesis, oocyte function and early embryonic development, and to identify objective molecular markers that are predictive of oocyte competence and subsequent potential reproductive success post-fertilization.
Our research program is centered around the development and application of hierarchical statistical models to inferential problems in animal breeding and genetics. Hierarchical Bayesian models are particularly useful for modeling multiple layers of variability and heterogeneity as characteristic of field data and genomics data. Our two broad areas of application are currently in 1) livestock genetic evaluation and 2) functional genomics. One recent specific application from our group has involved the genetic evaluation of calving ease, where models allowing for outlier-robustness and heterogeneous variability across environments (for example, herds) were found to fit field data much better than conventional genetic evaluation models. Other recent applications include the development of genetic evaluation models when uncertain paternity is common (as in extensive cattle production systems), and multi-breed genetic evaluations. Our current efforts are directed towards the construction of hierarchical models for the analysis of cDNA microarray data in the anticipation of better control over false negative and false positive rates on conclusions regarding differential gene expression. We also collaborate extensively with many other researchers on campus, particularly in the application of mixed effects and/or Bayesian model analyses to experimental and observational data.
Miriam S. Weber Nielsen, Associate Professor
Ruminant Metabolism Laboratory
Larry Chapin, Research Technician
Our research program focuses on identifying hormonal and nutritional factors that regulate growth and development of the bovine mammary gland. The emphasis of our current work is on evaluating development of the mammary gland in growing heifers and in response to changes in nutritional management. The laboratory also conducts work to identify factors that regulate proliferation of mammary epithelial cells in vitro. Research involves a variety of techniques including cell culture, immunocytochemistry, RT-PCR, cDNA microarrays, Northern blotting, Western blotting, ELISA, radioimmunoassay and others. The overall goal of our research is to identify strategies to more efficiently raise and manage dairy heifers to be productive lactating cows.