Steven C. Hand
Russell Thompson, Jr. Family Professor
Ph.D., Oregon State University,
1980
Bioenergetics, molecular
physiology, environmental control of gene expression,
comparative biochemistry
Lab Group
Michael Menze, Assistant Professor Research, menze@lsu.edu
Leaf Boswell, Ph.D. student, lboswe1@lsu.edu
Yuvraj Patil, Ph.D. student, ypatil1@lsu.edu
Julie Reynolds, Ph.D. student, jreyno3@lsu.edu
Trudy Witt, Ph.D. student, tlwitt@lsu.edu
Alex Combe, Undergraduate student, acombe2@lsu.edu
Philip Gilmore, Undergraduate student, pgilmo1@lsu.edu
Joy Norris, Undergraduate student, jnorri7@lsu.edu
Visit Hand
Lab
My research interests are integrative in that they require biochemical, cellular and organismic approaches to solve physiological questions. One current aim is to identify mechanisms that permit animals to enter, survive and exit states of hypometabolism and dormancy. For animals that enter quiescent states under anoxia, the duration of survival is correlated with the degree of metabolic depression. The length of anoxia tolerance increases by three orders of magnitude when ATP turnover under anoxia is depressed from 30% of aerobic values to 1%. Because conservation of energy is critical for survivorship, we are studying mechanisms for downregulating energetically expensive processes like gene expression (transciptional and translational levels), macromolecular turnover, and ion transport. Diapause is an interesting case of dormancy where environmental change is not a prerequisite for inducing the metabolic arrest in many species, but rather the cellular stasis is often developmentally programmed. Examples of diapausing organisms include insects, certain crustacean embryos (e.g., the brine shrimp Artemia franciscana), and embryos of annual killifish. Through the use of DNA microarray technology, we are beginning to evaluating the role of differential gene expression as a possible control mechanism for such states. The principles and mechanisms emerging from these studies of natural states of dormancy are being applied and investigated in mammalian cells with the goal of promoting the phenotype of cell stasis.
Many biochemical events must be triggered during entry into hypometabolic states, and in cases where an environmental ques are involved, mechanisms must be in place for sensing the variable (e.g., oxygen level). Evidence indicates that in many cells free heme and/or hemoproteins are intimately involved in oxygen sensing. Our experiments in this area are currently focusing on the characterization of a new molecular oxygen sensor within the mitochondrion of brine shrimp embryos that modulates protein synthesis during anoxia-induced quiescence. I anticipate that heme or hemoprotein sensors also may mediate oxygen sensing during exposure of certain marine/estuarine invertebrates to hypoxia. Reduction of plasma membrane conductivity for ions is recognized as another adaptive mechanism for conserving cellular energy under oxygen limitation. Until recently, however, the energetic advantage of reducing ion leaks through the mitochondrial inner membrane under severe hypoxia had not been considered. Evidence in the literature indicates that 30-40% of respiration in isolated hepatocytes is explained by mitochondrial proton leak. It follows that a substantial energy savings could accrue from restricting proton leak during hypoxia. In collaboration with Dr. Erich Gnaiger and his group at the University of Innsbruck, we are measuring the degree of mitochondrial coupling under conditions when oxygen supply to the mitochondrion is limiting, and our new data acquired with oxygen-injection microcalorimetry suggest that proton leak is indeed reduced. We observe high ADP/O ratios under hypoxia, which suggests an expanded role for the depression of membrane conductivity as an adaptive mechanism in hypometabolic states.
The energetics of symbioses between bacteria and invertebrates is another area of interest, which arose during previous studies of the hydrothermal vent communities along the Eastern Pacific Rise. More recently we have studied sulfur-based chemoautotrophic symbiosis involving the marine bivalve Lucina floridana from the northern gulf coast and the clam Lucinoma aequizonata from the Santa Barbara Basin (with colleagues from Scripps Institution of Oceanography). Cellular aspects of the metabolic interplay between host and bacterium hold numerous unanswered issues that we would like to explore. Identifying the signals that control the rates of synthesis and release of chemoautotropic synthate by the bacterial endosymbionts would improve our understanding of how these symbioses are metabolically coordinated.
A final area to briefly mention is ontogenetics changes in physiological traits of invertebrates. We have focused previously on the ontogeny of osmoregulatory capacities in estuarine shrimp and the timing of diapause in sponge gemmules. The ontogenetic acquisition of hypoxia tolerance is a key issue that deserves more exploration in marine invertebrates inhabiting oxygen limited environments.
Selected Publications
Hand, S.C., Jones, D., Menze, M.A., and Witt, T.L. (2006) Life without water: Expression of plant LEA genes by an anhydrobiotic arthropod. J. Exp. Zool. (in press).
Elliott, G., Liu, X-H, Cusick, J.L., Menze, M, Vincent, J., Witt, T , Hand, S. and M. Toner (2006) Trehalose uptake through P2X7 purinergic channels provides dehydration protection. Cryobiology 52: 114-127.
Liu, X-H., Aksan, A., Menze, M.A., Hand, S.C. and M. Toner (2005) Trehalose loading through the mitochondrial permeability transition pore enhances desiccation tolerance in rat liver mitochondria. Biochim. Biophys. Acta. 1717: 21-26.
Covi, J. and S.C. Hand (2005) V-ATPase expression during development of Artemia franciscana embryos: Potential role proton gradients in anoxia signaling. J. Exp. Biol. 208: 2783-2798.
Covi, J.A., Treleaven, W.D. and S.C. Hand (2005) V-ATPase inhibition prevents recovery from anoxia in Artemia franciscana embryos: Quiescence signaling through dissipation of proton gradients. J. Exp. Biol. 208: 2799-2808.
Menze, M.A., Hutchinson, K., Laborde, S.M. and S.C. Hand (2005) Mitochondrial permeability transition in the crustacean Artemia franciscana: Absence of a Ca2+ - regulated pore in the face of profound calcium storage. Amer. J. Physiol. 289: R68-R76
Menze, M.A., Clavenna, M. and S.C. Hand (2005) Depression of cell metabolism
and proliferation by membrane-permeable and -impermeable modulators: Role for
AMP-to-ATP ratio. Amer. J. Physiol. 288(2): R501-R510.
Return to the faculty index...