Key Life Science Research Programs at UMass Amherst
Biodiversity and Evolution: Comparative and Functional Genomics
The rapid development of the tools of molecular biology over the past several years has led to a vast amount of sequence. Research in the life sciences has moved beyond understanding the functions of individual genes, proteins and other small biological molecules to understanding how all of these molecules interact within cells and organisms. Functional genomics and comparative genomics are complementary activities that use an integration of experimental approaches and information technologies including bioinformatics to mine fundamental discoveries from genomic data. The ultimate goal is to gain new insights into the genetics and physiology of individual organisms and groups of organisms while deepening our understanding of the evolutionary relationships among organisms.
• Dr. Derek Lovley (Microbiology) has obtained over $23 million in external research funds since 1995 for the Geobacter Project. A major research focus in the Lovley lab is the genome-enabled investigation of the physiology of microorganisms involved in the anaerobic bioremediation of metal and organic contaminants. Geobacter species are being studied intensively in order to optimize practical applications such as the bioremediation of radioactive metals and harvesting electricity from waste organic matter. Other organisms with application to bioremediation and energy harvesting are being examined in a similar manner. These include the organism NaphS2, which serves as a model for the anaerobic degradation of polycyclic aromatic hydrocarbons in marine sediments and Rhodoferax ferrireducens, which is capable of effectively converting sugars to electricity in novel microbial fuel cells.
• UMass researchers led by Richard Yuretich (Geosciences) have received $1.6 million from the Biocomplexity in the Environment Program of the National Science Foundation.
The Chemistry-Biology Interface: Understanding and Engineering Biological Systems
Powerful tools and techniques of chemistry have increasingly opened doors to discovery in the biological sciences. Some UMass Amherst investigators use chemistry to dissect molecular interactions and pathways critical to cell function, while others are developing new therapeutic strategies and designing mimics of biological tissue.
• Vincent Rotello and Craig Martin (Chemistry) and Joe Jerry (Veterinary & Animal Science) are using chemical methods to design 'magic bullets' that selectively destroy breast cancer cells. In their NIH-supported research, surface-modified gold nanoparticles are targeted to the cancer cells, where they are internalized. Subsequently, the cells are killed either by microwave radiation or by toxic substances brought in by the nanoparticles.
• Lila Gierasch, Danny Schnell and Dan Hebert (Biochemistry and Molecular Biology), Lynmarie Thompson and Bob Weis (Chemistry), and Murugappan Muthukumar (Polymer Science & Engineering) use powerful chemical methods to explore the mechanisms of molecular movement and signal transmission across cellular membranes. Their research projects provide insight into regulation of cellular function by hormones and other signaling molecules, assembly of viruses in the cell, and functional defects in secretion leading to diseases such as albinism.
• Controlled expression of the genetic information encoded in cellular DNA lies at the heart of all biological processes. Robert Zimmermann, Skip Fournier, and Karsten Theis (Biochemistry & Molecular Biology) and Craig Martin (Chemistry) apply a wide variety of chemical approaches to explore the molecular machines involved in gene expression at atomic resolution. Understanding gene expression is essential to the development of treatments for viral infections, cancer, and many other disease states, and also contributes tools widely used in the biotechnology industry.
• Susan Roberts, Surita Bhatia, and Henning Winter (Chemical Engineering) and Maria Santore and Greg Tew (Polymer Science and Engineering) are using novel synthetic techniques to design polymeric materials that are tailored for specific biomedical applications. These researchers are developing nano- to micro- structured materials to encapsulate liver, thyroid, and islet cells for in vivo treatment of endocrine disorders and liver disease; polymers with properties similar to antimicrobial proteins; and highly elastic biocompatible gels with mechanical properties that mimic those of soft tissue.
Infection and Immunity
Organized societies protect their members against disease causing organisms through stringent public health measures including vaccination. However, even vigilant and well-prepared societies are vulnerable to the deliberate dissemination of highly virulent pathogens and to the emergence of novel pathogens for which no diagnostic tests and treatments are available. These new threats need to be countered by the development of effective and broadly-specific defenses against infectious agents. To encourage the scientific community to respond to this need, NIH supports research on “microbial biology and host responses to microbes; the development of new vaccines, therapies, and diagnostic tools; and the development of research resources such as appropriate laboratory facilities”. The UMass Amherst “Infection and Immunity” group, an interdepartmental body that focuses on human and animal infectious diseases including those targeted by the NIH, is working directly in this field.
• John Clark (Entomology) engineers pathogen-resistant vectors, specifically targeting the mosquito vector (Aedes aegypti) of dengue and dengue hemorrhagic fever viruses and head lice, which are vectors of epidemic typhus (Rickettia prowazekii).
• Cynthia Baldwin (Veterinary & Animal Science) evaluates mechanisms of host control of infectious disease organisms, specifically Brucella abortus, by identifying pathogen genes involved in virulence and host genes involved in response to those virulence factors.
• Lloyd Semprevivo (Veterinary & Animal Science), working with Intervet International, is developing vaccines and novel vaccine delivery systems against pathogenic viruses (human and simian immunodeficiency viruses), bacteria (Chlamydia) and parasitic worms (Fasciola hepatica).
• Barbara Osborne and Richard Goldsby (Veterinary & Animal Science) are developing therapeutics in vertebrate and invertebrate animal bioreactors, specifically large scale production of human immunoglobulins for passive transfer of protection against pathogens and toxins.
• Samuel Black (Veterinary & Animal Science) is developing immunostimulatory drones, ie., “stealth” liposomes that target inflammatory sites and enhance immune responses at those sites.
Life and Death of Cells: Neurodevelopment and Neurodegeneration
The nervous system is the most complex of all tissues, and until recently, it was assumed that treating neurological diseases resulting from developmental defects, injury or environmental influences was beyond the realm of practical science. Recent advances in cellular and molecular biology have changed this perspective. A highly integrated research team at UMass is providing key insights into how nervous systems develop, how specific pathways become damaged during disease, and how neural damage may be repaired. This group also includes several members who study damage and death of cells in muscle and the immune system in both animal models and humans. This research cluster works with the Baystate-UMass Biomedical Research Institute in Springfield to study degenerative disorders of nerve and muscle.
• Tom Zoeller (Biology) changed the field of developmental neurobiology with his demonstration that maternal thyroid hormone has profound effects on the development of the fetal nervous system. His recent work showing that environmental PCBs interfere with this process has profound implications for human health.
• Priscilla Clarkson (Exercise Science) is examining changes in gene expression in human muscle following injury and spinal cord injury to help define the molecular pathways that mediate muscle wasting. The proteins encoded by these genes may provide novel targets for therapeutic intervention.
• Larry Schwartz (Biology) was the first person to clone death-associated genes. The identification of these genes has provided new insights into degenerative disorders like Parkinson’s Disease as well as provide molecular tools for enhancing the survival of transplanted cells.
• Rolf Karlstrom (Biology) has used the power of zebrafish development to define critical events in the development of the nervous system. In collaboration with Baystate Medical Center clinicians, he is determining if mutations in these same genes are responsible for human birth defects.
• Geert Devries (Psychology) has demonstrated that hormones control the survival of specific neurons in males that regulate aggressive behavior.
Neuroendocrinology
Neuroendocrinologists study interactions between hormones and the brain. Hormones are an essential part of body-brain communication throughout life. Early in life, hormones guide normal brain development, orchestrate its sexual differentiation, and define stress responsiveness. In adulthood, hormones control processes such as reproduction, learning and memory, and eating and drinking. Hormonal dysfunction has been linked to a host of neurological and behavioral disorders, such as postpartum depression, premenstrual syndrome, and the progress of neuronal degenerative diseases such as Alzheimer. Finally, many environmental constituents such as industrial pollutants disrupt hormone-brain interactions, thereby causing, for example, mental retardation, fertility problems, and cancer. UMass Amherst has built an unusually strong cluster of neuroendocrinologists, centered around a prestigious NIH-funded Training Program. The following is a sampling of NIH-funded research activities of this cluster.
• Deborah Good (Veterinary and Animal Sciences) has discovered novel genes related to obesity. Deletion of these genes in mice generates animals that are grossly overweight. As so far only a handful of genes have been linked to obesity, Good’s research provides important new insights in factors controlling body weight. Good collaborates with George Wade (Psychology), who studies the role of neuropeptides in maintaining the balance between food intake and fertility. His research helps understand fertility problems in athletes as well as in people with eating disorders. Good’s expertise in molecular neuroscience and Wade’s in behavioral neuroscience complement each other and provide powerful new approaches to their respective research lines.
• Nancy Forger (Psychology) studies a sexually dimorphic system in the spinal cord of rats and mice in which cell death can be manipulated with gonadal hormones. During development the brain and spinal cord produces an abundance of motor neurons that innervate skeletal muscles, many of which will die in a naturally occurring process called programmed cell death. Although experiments with cells grown in culture suggest that growth factors are essential for motor neuron survival, it has been remarkably difficult to identify such factors in vivo. Using the process of sexual differentiaion, Forger has identifed growth factors and growth factor receptors necessary for survival of motoneurons. Her method provides a powerful strategy to study motorneuron cell death under physiological circumstances, which eventually should help to understand, and find cures for, muscular dystrophies.
• Forger collaborates with Geert De Vries (Psychology), who was the first to demonstrate a sex difference in the anatomy of neurotransmitter systems in the brain. Recently he demonstrated that such differences do not only cause differences in behavior, but prevent them as well. In the latter case these differences compensate for physiological and hormonal sex differences. Therefore, many behaviors that do not differ between males and females actually have sexually dimorphic neurochemical underpinnings. Such sex differences beg the development of sex-appropriate medication in neurological and behavioral disorders caused by imbalances of neurotransmitter systems.
• Tom Zoeller (Biology), Sandra Petersen (Biology), and Jeff Blaustein (Psychology) are mapping genes targeted by environmental constituents such as industrial pollutants polychlorinated biphenyls (PCBs) and compounds occurring naturally in food that act like hormones or disrupt hormone action. For example, Zoeller has demonstrated that genes targeted by thyroid hormone are also targeted by PCBs. As these genes are important for normal development of the cerebral cortex, his research explains how thyroid hormone guides normal development of the cortex as well as how PCBs can disrupt it. This type of research, therefore, helps explain the nature of the neurological damage done in people exposed to high levels of those compounds and may help prevent future harm done by such compounds.
Updated for FY05
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