DEPARTMENT OF BIOLOGY
INTEGRATIVE EXERCISE QUESTIONS
Faculty available to advise comps: Henderson, Hernández, Hougen-Eitzman, Jaramillo, McKone, Mitra, Rand, Singer, Tymoczko
1. (Tymoczko) Exercise is one of the most effective treatments for a host of pathological conditions including diabetes, coronary disease, hypertension, depression, and a variety of cancers. What are the biochemical foundations of these beneficial effects?
Hood, D. A. 2001. Contractile activity-induced mitochondrial biogenesis in skeletal muscle. Journal of Applied Physiology 90:1137-1157.
Roberts C.K., and R.J. Barnard. 2005. Effects of exercise and diet on chronic disease. Journal of Applied Physiology 98:3-30.
Wolin K. Y., Y. Yan, G.A. Colditz, and I.M. Lee. 2009 Physical activity and colon cancer prevention: a meta-analysis. British Journal of Cancer 100:611-616.
Chinsomboon, J., J. Ruas, R.K. Gupta, R. Thom, J. Shoag, G.C. Rowe, N. Sawada, S. Raghuraa, and Z. Arany. 2009. The transcriptional coactivator PGC-1a mediates exercise-induced angiogenesis in skeletal muscle. Proceedings of the National Academy of Sciences USA 106:21401-21406.
2. (Hernández) The effects of disturbance on ecological processes is at the foundation of the field of ecology. Understanding the effects of disturbance and the patterns of ecosystem recovery is important for determining the consequences of both natural and anthropogenic disturbances. Using a recent large disturbance as a case study (oil spill, hurricane, wildfire, disease outbreak, etc.), discuss the effects of disturbance on ecological processes, the mechanisms controlling the recovery of communities and ecosystems, and the long-term ecological consequences of disturbances.
Fraterrigo, J.M., and J.A. Rusak. 2008. Disturbance driven changes in the variability of ecological patterns and processes. Ecology Letters 11:756-770.
Keitt, T.H. 2008. Coherent ecological dynamics induced by large-scale disturbance. Nature 454: 331-335.
Spiller, D.A., and T.W. Schoener. 2007. Alteration of island food-web dynamics following major disturbance by hurricanes. Ecology 88:37-41.
3. (McKone) Ecologists are increasingly aware that there is no meaningful distinction between “ecological time” and “evolutionary time”. That is, evolutionary changes occur rapidly enough that contemporary ecological interactions are impacted. In particular, recent work on invasive species has demonstrated that evolutionary changes can occur both in an introduced species as it becomes invasive and in the native ecological community in response to interactions with newly introduced species. Review the role of evolutionary responses in the introduction and spread of invasive species.
Keller, S.R., and D.R. Taylor. 2008. History, chance and adaptation during biological invasion: separating stochastic phenotypic evolution from response to selection. Ecology Letters 11:852-866.
Llewelyn, J., B. L. Phillips, R. A. Alford, L. Schwarzkopf, and R. Shine. 2010. Locomotor performance in an invasive species: cane toads from the invasion front have greater endurance, but not speed, compared to conspecifics from a long-colonised area. Oecologia 162:343-348.
Pedersen, J. S., M. J. B. Krieger, V. Vogel, T. Giraud, and L. Keller. 2006. Native supercolonies of unrelated individuals in the invasive Argentine ant. Evolution 60:782-791.5.
4. (Singer) RNA binding proteins play important roles in posttranscriptional regulation in many species. The RNA binding proteins ELF9 and RBP50 regulate flowering time and long-distance transcript transport in plants, respectively; while, FMR1 RNA binding protein (FMRP) plays an important role in neurogenesis. Expansion of trinucleotide CGG repeats in the 5’ untranslated region of the FMR1 gene account for two more common neurodegenerative disorders. Fragile X mental retardation occurs when there are more than 200 CGG repeats and the gene is not transcribed and translated to produce the FMRP RNA binding protein. Fragile X-associated tremor/ataxia syndrome (FXTAS) is associated with 55-200 CGG repeats in the FMR1 gene, which when transcribed has a high affinity for RNA binding proteins, including FMRP. Choose and analyze an example of posttranscriptional regulation controlled by RNA binding proteins.
Ashley, C.T., K.D. Wilkinson, D. Reines, and S.T. Warren. 1993. FMR1 protein: conserved RNP family domains and selective RNA binding. Science 262: 563-566.
Brouwer, J.R., R. Willemsen, and B.A. Oostra. 2009. The FMR1 Gene and Fragile X-associated tremor/ataxia syndrome. American Journal of Medical Genetics Part B 150B:782-798.
Gessert, S., V. Bugner, A. Tecza, M. Pinker, and M. Kuhl. 2010. FMR1/FXR1 and the miRNA pathway are required for eye and neural crest development. Developmental Biology 341:222-235.
Ham, B., J.L. Brandom, B. Xoconostle-Cazares, V. Ringgold, T.J. Lough, and W.J. Lucas. 2009. A polypyrimidine tract binding protein, Pumpkin RB50, forms the basis of a phloem-mobile ribonucleoprotein complex. Plant Cell 21:197-215.
Shan, G., S. Xu, and P. Jin. 2008. FXTAS: A bad RNA and a hope for a cure. Expert Opinion on Biological Therapy 8:249-253.
Song, H., J. Song, J. Cho, R.M. Amasino, B. Noh, and Y. Noh. 2009. The RNA binding protein ELF9 directly reduces SUPPRESSOR OF OVEREXPRESSION OF CO1 transcript levels in Arabidopsis, possibly via nonsense-mediated mRNA decay. Plant Cell 21:1195-1211.
5. (Singer and Hougen-Eitzman) Global warming provides serious challenges to species. Depending on the degree to which animals and plants can adapt to changes in climatic zones and seasonal timing, widespread extinction could result. One type of adaptation involves changes in phenology (i.e., seasonal timing of life history events such as flowering or migration), which may be under both genetic and environmental control. It is unclear to what degree species are able to change their phenology, and what might be the ecological consequences of such changes. For this question, review and analyze either the control of phenological changes (genetic and/or environmental), or the ecological consequences of phenological changes)
Depending on your course background and interests you may choose to pursue this question with either a genetic or an evolutionary ecological emphasis. For example, a genetic emphasis might involve an analysis of genetic networks that integrate photoperiod, vernalization, gibberellin, and autonomous pathways to flowering. These networks are based on forward genetic screens, microarray analysis, QTL mapping studies, and candidate gene association mapping. You would evaluate the current models for the regulation of flowering and assess their potential applicability to understanding the evolutionary ecology of flowering time. With an ecological emphasis, the focus on complexity and interaction would be at the level of organisms and their environment.
Baurle, I., and C. Dean. 2006. The timing of developmental transitions in plants. Cell 125: 655-664.
Ehrenreich, I.M, Y. Hanzawa, L. Chou, J.L. Roe, P.X. Kover, and M.D. Purugganan. 2009. Candidate gene mapping of Arabidopsis flowering time. Genetics 183: 325-335.
Cleland, E.E., I. Chuine, A. Menzel, H.A. Mooney, and M.D. Schwartz. 2007. Shifting plant phenology in response to global change. Trends in Ecology & Evolution 22:357-2365.
Kaufmann, K., F. Wellmer, J.M. Muino, T. Ferrier, S.E. Wuest, V. Kumar, A. Serrano-Mislata, Madueno, P. Krajewski, E.M. Meyerowitz, G.C. Angenent, and J.L. Riechmann. 2010. Orchestration of floral initiation by APETALA1. Science 328: 85-889.
Pulido, F., and P. Berthold. 2010. Current selection for lower migratory activity will drive the evolution of residency in a migratory bird population. Proceedings of the National Academy of Sciences USA 107:7341-7436.
6. (Henderson) One goal in drug design is to create a potent drug that hits a single target. However, several diseases are multifactorial, in that their pathogenesis results from the disruption of more than one gene, protein, or pathway. Select from the multitude of such complex disorders, which include but are not limited to Alzheimer’s disease, epilepsy, diabetes, multiple sclerosis, schizophrenia, manic depression, asthma, rheumatoid arthritis, and the common cancers, such as breast, bowel, and ovarian cancers. Describe multiple disruptions that lead to the selected disease and discuss the implications for creating a single molecular target in this particular disease.
De Strooper, B. 2010. Proteases and proteolysis in Alzheimer disease: A multifactorial view on the disease process. Physiological Reviews 90:465-494.
7. (Mitra) One of the best-studied symbioses is that between legume plants and rhizobial bacteria. This symbiosis allows plants to grow in nitrogen-poor soils, as the symbiotic bacteria reduce molecular nitrogen for plant use. In turn, plants build a novel organ on their roots, termed the root nodule, within which rhizobia are housed and protected. Within the past decade, many plant proteins have been identified that function in the nodulation pathway. These proteins play a variety of roles during symbiotic development whether in nodulation signaling, infection progression or nodule functioning. Focus upon a set of plant proteins that control a specific part of the symbiotic pathway. Examine how these proteins control symbiotic development, and identify open questions that remain in the field.
Oldroyd GE, J.A. Downie. 2008. Coordinating nodule morphogenesis with rhizobial infection in legumes. Annual Review of Plant Biology 59:519-46.
Crespi M, and F. Frugier. 2008. De novo organ formation from differentiated cells: root nodule organogenesis. Science Signaling 1(49):re11.
8. (Rand and Jaramillo) Natural behaviors such as drinking, eating, and sexual activity are reinforced by neural circuitry collectively called the reward system. Several brain nuclei and neurotransmitter systems are known or hypothesized to be part of, or act upon, the reward circuitry. Much of our knowledge of this system stems from investigations into addiction, a common pathology involving this system. Review the current literature regarding a specific neurophysiological subset of the reward system or choose a specific behavior or pathology that influences or is influenced by the reward circuits.
Kauer, J.A., and R.C. Malenka. 2007. Synaptic plasticity and addiction. Nature Reviews Neuroscience 8: 844-858.
Le Merrer, J., J.A.J. Becker, K. Befort, and B.L. Kieffer. 2009. Reward processing by the opioid system in the brain. Physiological Reviews 89:1379-1412.
Solinas, M., C. Chauvet, N. Thiriet, R. El Rawas, and M. Jaber. 2008. Reversal of cocaine addiction by environmental enrichment. Proceedings of the National Academy of Sciences USA 105:17145-17150.
9. (Rand) Chemical communication among organisms can take on many forms; from allelopathy and pollinator pheromone mimicry in plants to the pheromonal manipulation of reproduction and behavior in conspecifics. Insect and mammalian pheromone systems are among the best studied and offer an interesting peek into the mechanisms of olfactory reception, neural signaling, and the resulting behavioral or reproductive changes in the receiving individual. Review the recent literature regarding a specific inter-organismal chemical communication system and describe the mechanisms that influence the reproductive physiology or behavior of the receiver.
Boehm, U., Z. Zou, and L.B. Buck. 2005. Feedback loops link odor and pheromone signaling with reproduction. Cell 123:683-695.
Pankevich, D.E., M.J. Baum, and J.A. Cherry. 2004. Olfactory sex discrimination persists, whereas the preference for urinary odorants from estrous females disappears in male mice after vomeronasal organ removal. Journal of Neuroscience 24:9451-9457.
Stern, K. and M.K. McClintock. 1998. Regulation of ovulation by human pheromones. Nature 392:177-179.
Tirindelli, R., M. DiBattista, S. Pifferi, and A. Menini. 2009. From pheromones to behavior. Physiological Reviews 89:921-956.
10. (Jaramillo) Damage to hair cells, the mechanosensory receptors of the vestibular and auditory systems, is responsible for some of the most common balance and hearing disorders. Hair cells in mammals have only a very limited capacity for regeneration. Therefore, a sustained effort to understand regeneration and the factors that limit this capability has taken place over the last decade. Review the current state of knowledge of the hair cell regeneration field and identify the most promising therapeutic avenues for regeneration in mammals.
Millimaki, B.B., E.M. Sweet, and B.B. Riley. 2010. Sox2 is required for maintenance and regeneration, but not initial development, of hair cells in the zebrafish inner ear. Developmental Biology 338:262-269.
Praetorius, M., C. Hsu, D.E. Brough, P. Plinkert, and H. Staecker. 2010. Adenovector-mediated hair cell regeneration is affected by promoter type. Acta Otolaryngologica 130:215-222.
Behra, M., J. Bradsher, R. Sougrat, V. Gallardo, M.L. Allende, and S.M. Burgess. 2009. Phoenix is required for mechanosensory hair cell regeneration in the zebrafish lateral line. PLoS Genetics 5:e1000455.
Baker, K., D.E. Brough, and H. Staecker. 2009. Repair of the vestibular system via adenovector delivery of Atoh1: a potential treatment for balance disorders. Advances in Otorhinolaryngology 66:52-63.