INTEGRATIVE EXERCISE QUESTIONS


Faculty available to chair comps committees: Camill, Hougen-Eitzman, Jaramillo, McKone, Rand, Tymoczko, Wagenbach (accelerated fall comps only), and Zweifel

1. (Tymoczko) Although it has been established for centuries that oxygen is essential for most life forms, it is only recently that we have begun to understand how cells sense and respond to hypoxia. In general, it is clear that hypoxia results in increase in the cells anaerobic metabolic capacity as well as an increase in the mechanisms of delivering oxygen to tissues. Understanding the Hypoxia Response Pathway will have important impacts on a diverse array of subjects, including metabolic response to exercise, cancer, myocardial infarction, and programmed cell death. Review what is known about the Hypoxia Response Pathway, and discuss the cellular and organismal oxygen sensors and their mechanism of signaling.

Semenza, G.L. 2001. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell 107:1-3
Hoppeler, H., and M. Vogt. 2001. Muscle tissue adaptations to hypoxia. The Journal of Experimental Biology 204:3133-9.
Semenza, G. L. 2001. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends in Molecular Medicine 7:345-50.
Prabhakar, N.R. 2001. Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 90:1986-94.
Hoppeler, H., and M. Vogt. 2001. Hypoxia training for sea-level performance. Training high-living low. Advances in Experimental Medicine and Biology 502:61-73.

2. (Tymoczko) The process of dissemination of a malignant tumor to distant sites to form secondary tumors (metastasis) is a complex and dynamic process. Many cellular processes are required. The cell must recognize when growth and division are required or when migration should be initiated. These molecular responses include production or recruitment of growth factors, migration stimulants and proteases. Review what is known about the metastatic process. Discuss how this is controlled and how the process of metastasis might be interrupted

Hahn, W.C., and R.A. Weinberg. 2002. Rules for making human tumor cells. The New England Journal of Medicine 347:1593-1603.
Hanahan, D., and R.A. Weinberg. 2000. The hallmarks of cancer. Cell 100:57-70.

3. (Jaramillo) Auditory hallucinations are a common symptom of schizophrenic patients. Until recently these have not been studied in detail but modern imaging techniques are starting to allow progress in the study of this poorly understood phenomenon. Describe recent work that seeks to address this issue, and put these findings within the overall context of the disease.

Hoffman, R.E., et. al. 2003. Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations. Arch Gen Psychiatry 60:49-56.

4. (Jaramillo) Several pathogenic organisms have an amazing ability to utilize their host’s cytoskeleton to achieve their evil purposes. Review the cellular and molecular mechanisms that enable these pathogens to subvert their victim’s cytoskeleton to their advantage.

Hyward, R.D., and V. Koronakis. 2002. Direct modulation of the host cell cytoskeleton by Salmonella actin binding proteins. 2:15-20
Rafelski, S.M., and J.A. Theriot. 2001. A hitchhiker’s guide to cell biology: exploitation of host-cell functions by intracellular pathogens. Genome Biology 3(3):REPORTS4006.
This is Julie Theriot’s movies page at Stanford. Several important references (including Rafelski’s) are listed in her home page.

5. (Camill) In 1960, Hairston, Smith, and Slobodkin posed the “Earth is Green” hypothesis, suggesting that autotrophic biomass is not completely mowed down by herbivores because herbivores are, in turn, regulated strongly by predators (also known as “top-down” trophic regulation). Other research suggests possible “bottom-up” control, whereby the number of individuals (or biomass) in higher trophic levels is controlled predominantly by the production of biomass at lower trophic levels (or by nutrients in the case of plants). More recently, the debate has become a central question in global change research for understanding issues as diverse as the loss and restoration of large mammals in parks, control of algae in eutrophic lakes, and the effects of fish overharvesting on marine reef systems. This question is two-part: First, based on field evidence, is there a current consensus for top-down vs. bottom-up trophic regulation in ecosystems? Feel free to focus on a particular ecosystem type (terrestrial, wetland, freshwater, or marine), or you may chose a comparative approach to determine if regulation varies systematically across ecosystems. What impact does consensus or lack thereof have on our understanding of how ecosystems function? Second, analyze a current, data-rich conservation issue to show how an understanding of trophic regulation is critical for the long-term management of that ecosystem.

Shears, N.T., and R.C. Babcock. 2002. Marine reserves demonstrate top-down control of community structure on temperate reefs. Oecologia 132:131-142.
Terborgh, J., Lopez, L. and P. Nunez, et al. 2001. Ecological meltdown in predator-free forest fragments. Science 294:1923-1926.
Silliman B.R., and M.D. Bertness. 2002. Atrophic cascade regulates salt marsh primary production. Proceedings of the National Academy of Science USA 99:10500-10505.
Shurin, J.B., E.T. Borer, E.T. and E.W. Seabloom, et al. 2002. A cross-ecosystem comparison of the strength of trophic cascades. Ecology Letters 5:785-791.

6. (McKone) Species diversity has been the focus of considerable debate in ecology. Some have argued that species diversity has a profound impact on the functional characteristics of communities, while others conclude that species diversity can vary greatly with little impact on communities. Review the ideas and experimental evidence in this debate.

Chapin, F. S., III, E. S. Zavaleta, V. T. Eviner, R. L. Naylor, P. M. Vitousek, H. L. Reynolds, D. U. Hooper, S. Lavorel, O. E. Sala, S. E. Hobbie, M. C. Mack, and S. Díaz. 2000. Consequences of changing biodiversity. Nature 405:234-242.
Naeem, S. 2002. Ecosystem consequences of biodiversity loss: The evolution of a paradigm. Ecology 83:1537-1552.

7. (Hougen-Eitzman) Cytochrome P450 enzymes comprise a large family of enzymes present in both eukaryotes and prokaryotes. They play a large role in the interactions between plants and insects: plants use them to synthesize antiherbivore chemicals and herbivores use them to detoxify these same chemicals. These enzymes are also important in the evolution of insect resistance to pesticides. Examine the how the regulation of these P450 enzymes affects plant-insect relationships or the evolution of pesticide resistance.

Li, X., Schuler, M.A., and M.R. Berenebaum. 2002. Jasmonate and salicylate induce expression of herbivore cytochrome P450 genes. Nature 419:712-715.
Boivin, T., Bouvier, J.C., Chadoeuf, J., Beslay, D.,and B. Sauphanor. 2003. Constraints on adaptive mutations in the codling moth Cydia pomonella (L.): measuring fitness trade-offs and natural selection. Heredity 90:107-113.
Daborn, P.J., Yen, J.L., Bogwitz, M.R., Le Goff, G., Feil, E., Jeffers, S., Tijet, N., Perry, T., Heckel, D., Batterham, P., Feyereisen, R., Wilson, T.G., and R.H. Ffrench-Constant. 2002. A single P450 allele associated with insecticide resistance in Drosophila. Science 297:2253-2256
Scott, J.G., and Z. Wen. 2001. Cytochromes P450 of insects: the tip of the iceberg. Pest Management Science 57:958-967.

8. (Zweifel/McKone) In most biological systems, genetic information is stored in DNA sequences and transcribed into RNA sequences in the process of gene expression. However, the enzyme reverse transcriptase catalyzes the reverse flow of information, from RNA to DNA. Discuss one or more of the following:
– the function and molecular mechanism of reverse transcriptase action in organisms with a DNA genome.
– the evolutionary origin of reverse transcriptase.
– the distribution of reverse transcriptase across life on Earth.
– the relationship of elements that have reverse transcriptase (including, e.g., retroviruses and retrotransposons).

Eickbush, T.H. 1997. Telomerase and retrotransposons: Which came first? Science 277:911-912.
Lundblad, V. 1998. Telomerase catalysis: a phylogenetically conserved reverse transcriptase. Proceedings of the National Academy of Sciences USA 95:8415-8416.
Ovchinnikov, I., A. Rubin, and G. D. Swergold. 2002. Tracing the LINEs of human evolution. Proceedings of the National Academy of Sciences USA 99:10522-10527.

9. (McKone) The discovery of the structure of DNA 50 years ago has had a profound impact on all areas of biology. Previously, evolutionary biologists based their reconstruction of evolutionary events on morphological characteristics of extant and fossil organisms. DNA sequences offer a massive new data set which can be used to determine the phylogeny of living organisms and the timing of evolutionary events (via “molecular clocks”). Though many traditional evolutionary patterns have been supported by DNA sequence data, there are some cases where such data have caused a radical reassessment of previous hypotheses. Choose a group or groups where DNA evidence has been used to challenge earlier ideas, and evaluate the debate that has ensued.

Murphy, W. J., E. Eizirik, S. J. O’Brien, O. Madsen, M. Scally, C. J. Douady, E. Teeling, O. A. Ryder, M. J. Stanhope, W. W. de Jong, and M. S. Springer. 2001. Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science 294:2348-2351.
Zanis, M. J., D. E. Soltis, P. S. Soltis, S. Mathews, and M. J. Donoghue. 2002. The root of the angiosperms revisited. Proceedings of the National Academy of Sciences USA 99:6848-6853.
Zardoya, R., and A. Meyer. 2001. The evolutionary position of turtles revised. Naturwissenschaften 88:193-200.

10. (Rand) During development, environmental factors (e.g. temperature, pH, and/or hydration state) or the inheritance pattern of genetic factors (e.g. SRY or DMRT-1) have been shown to direct the differentiation of the bipotential gonads into either testes or ovaries. These differentiated gonads secrete peptide and steroid hormones which then direct the development of the remaining sexual phenotype, including neurological structures that influence behavior. This has been the working hypothesis for the production of brain sexual dimorphisms and sexually dimorphic behavior over the last 50 years. However, recent evidence from a growing number of vertebrate species indicates that the gonadal steroid-brain dimorphism “dogma” may have been a bit premature. Studies with lab mice, zebra finches, and the red-eared slider (turtle) suggest that sexual dimorphisms within the brain may develop independently of gonadal steroids and that in some cases the brain produces its own steroids de novo. Examine the molecular and steroidogenic mechanisms involved with brain sexual differentiation in one or more of these model systems and provide a critical evaluation of research in this area.

Agate, R.J., W. Grisham, J. Wade, S. Mann, J. Wingfield, C. Schanen, A. Palotie, and A.P. Arnold. 2003. Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch. Proceedings of the National Academy of Sciences USA 100:4873-4878.
Carruth, L.L., I. Reisert, and A.P. Arnold. 2002. Sex chromosome genes directly affect brain sexual differentiation. Nature Neuroscience 5:933-934.
Crews, D., A. Fleming, W.E. Baldwin, and J.K. Skipper. 2001. Role of steroidogenic factor 1 and aromatase in temperature-dependent sex determination in the red-eared slider turtle. Journal of Experimental Zoology 290:597-606.