Cell biology

Joan Curry, PhD, stands in the field of research related to interfacial chemistry, which is a focus within physical chemistry. Within interfacial chemistry, she focuses on chemistry of molecules at the interfaces where solids and liquids come together. The term solid here includes mineral and bacterial surfaces found in soils and sediments, metal and oxide machine surfaces and cell surfaces found in the human body. Molecules can be water and ions that bathe soil surfaces, organics that lubricate machine parts and large biomacromolecules, such as proteins and lipopolysaccharides, attached to cells that mediate cell adhesion. Her specific interests are: 1) determining the effect of confinement on liquids in general and lubricants in particular and 2) characterizing the adhesive properties of cell surface biomacromolecules. The primary goal of this work is to understand how biomacromolecules that cover cell surfaces influence the interaction and adhesion of cells with other cells and with solid surfaces. Cells can be either bacteria or human cells. It is important to understand bacterial adhesion because it is the first step in biofilm formation, which has numerous undesirable consequences ranging from heat exchanger fouling to medical implant infections. Currently, very little is known about how bacterial surface biomacromolecules mediate adhesion and therefore it is still not possible to control or manipulate the process. Human cell adhesion is also mediated by biomacromolecules, in particular proteins that bind to one another through specific lock and key mechanisms. The structure of many cell adhesion proteins is well known but their function is still poorly understood. In collaboration with Ronald Heimark (Surgery), Dr. Curry is working to understand how heavy metals such as cadmium affect the binding of cell adhesion proteins called cadherins. This work will help scientists understand better how heavy metals may lead to birth defects and in adults could accelerate cardiovascular disease. This work is experimental and involves direct force measurements between biomembrane covered mica surfaces with the Surface Forces Apparatus (SFA). With the SFA it is possible to measure the magnitude and distance dependence of molecular forces acting between two flat surfaces with angstrom and nanonewton resolution.

Matthew Cordes, Ph.D. is an Associate Professor of Chemistry and Biochemistry at the University of Arizona College of Science. Dr. Cordes’ research focuses on the origin and evolution of new protein structures and functions. He has published approximately 30 original research papers and presents his work frequently at national meetings such as the Protein Society and Gordon Research Conferences on Proteins and Biopolymers. Dr. Cordes’ primary research contributions are in four fields of protein evolution. First, his laboratory has identified cases in which a new type of protein structure has evolved from a preexisting structure. Second, he has identified evolutionary codes by which proteins that bind specific sites on double-stranded DNA evolve to recognize new target sites. Third, he studies the evolution of proteins in bloodsucking insects and spiders that affect blood homeostasis or cause dermonecrotic effects in mammalian tissue. Finally, he uses bioinformatics to identify hidden patterns in protein sequences that allow them to fold correctly and avoid aggregation such as that which occurs in Alzheimer’s disease. Dr. Cordes presently holds a BIO5 pilot project seed grant to study the evolution of enzyme toxins in brown spider venom.

Our research focuses on the signal transduction pathways and molecular mechanisms controlling directed cell migration, or chemotaxis, in eukaryotic cells. Chemotaxis is central to many biological processes, including the embryonic development, wound healing, the migration of white blood cells (leukocytes) to sites of inflammation or bacterial infection, as well as the metastasis of cancer cells. Cells can sense chemical gradients that are as shallow as a 2% difference in concentration across the cell, and migrate towards the source of the signal, the chemoattractant. This is achieved through an intricate network of intracellular signaling pathways that are triggered by the chemoattractant signal. These pathways ultimately translate the detected chemoattractant gradient into changes in the cytoskeleton that lead to cell polarization and forward movement. In addition, many cells such as leukocytes and Dictyostelium, transmit the chemoattractant signal to other cells by themselves secreting chemoattractants, which increases the number of cells reaching the chemoattractant source.To investigate key mechanisms of signal transduction underlying chemotaxis, we are using the social amoeba Dictyostelium discoideum as well as human cancer cell models. Cell motility and chemotaxis of Dictyostelium cells is very similar to that of leukocytes and cancer cells, using the same underlying cellular processes as these higher eukaryotic cells. Dictyostelium is amenable to cell biological, biochemical, and genetic approaches that are unavailable in more complex systems. The discoveries we make using Dictyostelium are then confirmed in human cells and, in particular, in the context of directed cancer cell migration and metastasis. Our aim is to understand the molecular foundation of directed cell migration, which is expected to guide the design of efficient anti-metastatic treatments.Our approach is interdisciplinary, in which we combine molecular genetics and proteomics to identify new signaling proteins and pathways involved in the control of chemotaxis, with live cell imaging using fluorescent reporters to understand the spatiotemporal dynamics of the signaling events, as well as biochemical analyses and proximity assays [including Bioluminescence Resonance Energy Transfer (BRET) and FRET] to understand how proteins interact and function within the signaling network. In addition, in collaboration with Dr. Wouter-Jan Rappel at UC San Diego, we generate quantitative models of the chemotactic signaling networks to help identify key regulatory mechanisms and link them to whole cell behavior

Andrew Capaldi, PhD, researches the signaling pathways and transcription factors in a cell that are organized into circuits. They allow cells to process information and make decisions. For Dr. Capaldi, the work arises in understanding both how these circuits are built from their components, and how they function and malfunction. To address these questions, he is working to reverse engineer the circuitry that controls cell growth in budding yeast using a combination of genomic, proteomic and computational methods. http://capaldilab.mcb.arizona.edu

The control of gene expression is critical to nearly all aspects of cellular biology, from maintaining basic cell function and identity, to the ability of cells to respond to numerous signals that arise during processes such as development, exposure to pathogens or changes in the cellular environment. A key means by which all cells enact appropriate gene expression responses is to alter the function of messenger RNAs (mRNAs). mRNAs exist in different functional states, dependent upon the proteins bound to them. These states include translation (protein synthesis), repression (off state) and decay. The localization of an mRNAs can also affect its function, thus cells are offered an array of spatial and temporal mechanisms for gene expression control at the mRNA level. mRNAs can also cycle between these different functional states. For example, mRNAs exiting translation often accumulate in distinct mRNA-protein (mRNP) assemblies known as P-bodies and stress granules, from which they may ultimately return to translation again or possibly undergo mRNA decay. Dr Buchan (Ph.D, B.S.) and his lab are particularly interested in the study of P-bodies and stress granules. These conserved, mRNA-protein (mRNP) bodies contain important protein regulators of mRNA decay and translation, as well as signaling proteins, and thus affect gene expression control and cell signaling pathways. In addition, they strongly resemble other important mRNP granules that function in embryogenesis (maternal granules) and memory formation (neuronal transport granules). Finally, stress granules and P-bodies have numerous connections to disease, such as an involvement in RNA viral replication, elevated levels in certain cancer types, as well as the formation of aberrant stress granules in neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The Buchan lab uses yeast and cell line models to study the assembly, disassembly and function of stress granules and P-bodies, and how aspects of stress granule and P-bodies contribute to ALS and forms of cancer

Dr. Scott Boitano Ph.D., is a Professor of Physiology, Cellular and Molecular Medicine, the BIO5 Institute and Associate Research Scientist of the Arizona Respiratory Center. Dr. Boitano received a B.S. in Plant Biology from University of California; Berkeley and a Ph.D. in Genetics & Cell Biology from Washington State University. Dr. Boitano’s primary research interest is in cell respiration. This encompasses the analysis and observation of cell physiology, cell-cell communications and cell-pathogen interactions. Dr. Boitano’s research pertains to the upper airway epithelium is an active cellular layer with ciliary movement to clear materials, the ability to secrete inflammatory effectors, and a biological barrier function that helps protect against pathogenic microorganisms, foreign insults and injury. Although much is known concerning the microbial genetics and microbial signaling of infection by Bordetella, relatively little is known about host cell pathology after exposure to Bordetella. Individuals have a primary tissue culture system that serves as an in vitro model of airway cell signaling and communication, and a battery of B. bronchiseptica strains, some of which are mutant in key factors shown to inhibit their ability to establish infection in animal models. His research goal is to define specific pathogen factors that alter host cell physiology to initiate or overcome host cell defense. The Boitano lab also analyzes the layers of the alveoli of the distal mammalian lung. Minimal information is known about this subject and Dr. Boitano believes that this model system for alveolar intercellular communication could expedite the formulating and testing of new medical treatments for dysfunctional alveolar cell physiology that underlies specific airway conditions following disease, insult and injury in the lung.

Parker Antin is Professor of Cellular and Molecular Medicine in the College of Medicine, Associate Vice President for Research for the Division of Agriculture, Life and Veterinary Medicine, and Cooperative Extension, and Associate Dean for Research in the College of Agriculture and Life Sciences. In his positions of Associate Vice President and Associate Dean, he is responsible for developing and implementing the research vision for the Colleges of Agriculture and Life Sciences and the College of Veterinary Medicine, with total research expenditures of approximately $65M per year. His responsibilities include oversight of research strategy and portfolio investment, grants and contracts pre award services, research intensive faculty hires and retentions, research communication and marketing, research facilities, and research compliance services. In collaboration with Division and College leadership teams, he has shared responsibilities for philanthropy, budgets and information technology. Dr. Antin is a vertebrate developmental biologist whose research is concerned with the molecular mechanisms of embryonic development. His research has been supported by NIH, NSF, NASA, USDA, and the DOE, as well as several private foundations including the American Heart Association and the Muscular Dystrophy Association, He is the Principal Investigator of CyVerse, a $115M NSF funded cyberinfrastructure project whose mission is to design, deploy and expand a national cyberinfrastructure for life sciences research, and train scientists in its use (http://cyverse.org). With 65,000 users worldwide, CyVerse enables scientists to manage and store data and experiments, access high-performance computing, and share data and results with colleagues and the public. Dr. Antin is also active nationally in the areas of science policy and funding for science. He is a past President of the Federation of Societies for Experimental Biology (FASEB), an umbrella science policy and advocacy organization representing 32 scientific societies and 135,000 scientists. His continued work with FASEB, along with his duties as Associate Vice President and Associate Dean for Research, and CyVerse PI, brings him frequently to Washington, DC, where he advocates for support of science and science policy positions that enhance the scientific enterprise.