INTEGRATIVE EXERCISE QUESTIONS

Faculty members available for both fall/winter and winter/spring: Henderson, Hougen-Eitzman, McKone, Mitra, Rand, Singer, Wolff, and Zweifel. Available only fall/winter: Walser-Kuntz. Available only winter/spring: Jaramillo.

1. (Mitra) Plants and microbes use energy from sunlight to synthesize a variety of molecules that can be used to produce biofuels for human use. Plant cell walls contain carbohydrates that can be fermented to produce ethanol; plant seeds contain lipids that can be made into diesel fuel; photosynthesizing bacteria produce hydrogen gas. Review the literature on biofuels, focusing upon the biochemical pathways required to produce and extract biofuels for human use. Additionally, make a recommendation for a target for genetic engineering that will improve biofuel availability.

Himmel M.E., S.-Y. Ding, D. K. Johnson, W. S. Adney, M. R. Nimlos, J. W. Brady, T. D. Foust. 2007. Biomass recalcitrance: engineering plants and enzymes for biofuels production. Science 315:804-807.

Ragauskas, A. J., C. K. Williams, B. H. Davison, G. Britovsek, J. Cairney, C. A. Eckert, W. J. Frederick, Jr., J. P. Hallett, D. J. Leak, C. L. Liotta, J. R. Mielenz, R. Murphy, R. Templer, and T. Tschaplinski. 2006. The path forward for biofuels and biomaterials. Science 311:484-489.

Stephanopoulos, G. 2007. Challenges in engineering microbes for biofuels production. Science 315:801-804.

2. (Hougen-Eitzman) Carbon dioxide levels in the atmosphere have been increasing since the beginning of the industrial revolution. Certainly these recent changes are anthropogenic, however it remains to be seen how rising CO2 levels will affect the physiology and ecology of organisms, or the functioning of ecosystems. Examine the effects of increasing atmospheric CO2 levels (disregarding temperature change) on plant or animal biology, and/or ecosystem properties (including carbon flux).

Lal, S. 2004. Soil carbon sequestration impacts on global climate change and food security. Science 304:1623-1627.

Leakey, A. D. B., F. Xu, K. M. Gillespie, J. M. McGrath, E. A. Ainsworth, and D.R. Ort. 2009. Genomic basis for stimulated respiration by plants growing under elevated carbon dioxide. Proceedings of the National Academy of Sciences, USA 106:3597-3602.

Rhemtulla, J. M., D. J. Mladenoff, and K. C. Murray. 2009. Historical forest baselines reveal potential for continued carbon sequestration. Proceedings of the National Academy of Sciences, USA 106:6082-6087.

Rosa, R., and B.A. Seibel. 2008. Synergistic effects of climate-related variables suggest future physiological impairment in a top oceanic predator. Proceedings of the National Academy of Sciences, USA 105:20776-20780.

Zavala, J.A., C.L. Casteel, E.H. DeLucia, and M.R. Berenbaum. 2008. Anthropogenic increase in carbon dioxide compromises plant defense against invasive insects. Proceedings of the National Academy of Sciences, USA 105:5129-5133.

3. (Wolff and Singer) The development of a complex organism from a single cell requires precise regulation of thousands of genes that control processes such as cell division, patterning, fate specification and differentiation. Recent studies suggest that microRNAs (miRNAs) are crucial regulators of gene expression in many developmental contexts, including embryonic stem cells, gastrulation, Hox-mediated patterning, and genesis of neurons, heart, muscle, and immune cells in animals. The centrality of miRNAs in plant development is evidenced by defective leaf, floral, and ovule phenotypes. Explore how a miRNA or family of miRNAs regulates development of a specific organ or embryonic structure.

Gangaraju, V. K., and H. Lin. 2009. MicroRNAs: key regulators of stem cells. Nature Reviews Molecular Cell Biology 10:116-125

Kiefer, J. C. 2006. microRNAs under the microscope. Developmental Dynamics 235:846-853.

Stefani, G., and F. J. Slack. 2008. Small non-coding RNAs in animal development. Nature Reviews Molecular Cell Biology 9:219-230.

Willmann, M. R., and R. S. Poethig. 2007. Conservation and evolution of miRNA regulatory programs in plant development. Current Opinion in Plant Biology 10:503-511.

Yang, T., L. Xue, and L. An. 2007. Functional diversity of miRNA in plants. Plant Science. 172:423-432.

Yekta1, S., C. J. Tabin, and D. P. Bartel. 2008. MicroRNAs in the Hox network: an apparent link to posterior prevalence. Nature Reviews Genetics 9:789-796.

4. (Jaramillo – Winter/Spring only) Diffuse modulatory neurotransmitter systems exert a powerful influence on many functions of the brain. For example, the noradrenergic diffuse modulatory system is involved in the regulation of attention, arousal, sleep cycles, memory, anxiety, pain and mood. Review the actions of one of the following transmitter’s diffuse actions on the brain: norepinephrine, serotonin, acetylcholine, dopamine, or histamine. You may focus your attention on a small number of issues (e.g. attention, addiction, memory, anxiety, etc.).

Jones, B. E. 2008. Modulation of cortical activation and behavioral arousal by cholinergic and orexinergic systems. Annals of the New York Academy of Sciences 1129:26-34.

Engleman, E. A., Z. A. Rodd, R. L. Bell, and J. M. Murphy. 2008. The role of 5-HT3 receptors in drug abuse and as a target for pharmacotherapy. CNS & Neurological Disorders Drug Targets 7:454-467.

Boulougouris, V. and E. Tsaltas. 2008. Serotonergic and dopaminergic modulation of attentional processes. Progress in Brain Research 172:517-542.

Williams, M. J., and B. Adinoff. 2008. The role of acetylcholine in cocaine addiction. Neuropsychopharmacology 33: 1779-1797.

5. (Zweifel) Consider RNA’s sad life as a supporting player to DNA when Francis Crick uttered the famous central dogma of biology: “DNA makes RNA makes protein”. Aside from some crucial roles in translation and splicing, RNA has been historically relegated to the role of playing the intermediary between gene and protein. But every dog has its day, and recent findings that huge sections of the mammalian genome are transcribed, suggests that RNA has continued to evolve and expand alongside proteins and DNA. Termed long non-coding RNAs (ncRNAs), these developmentally regulated transcripts may play a significant role in the genetic programming of complex organisms, and in disease etiology. Examine the function of long ncRNAs and how they might influence gene expression at the level of chromatin remodeling, transcriptional control, and post-transcriptional processing.

Carninci, P., et al. 2005. The transcriptional landscape of the mammalian genome. Science 309:1559-1563.

Mercer, T. R., M. E. Dinger, and J. S. Mattick. 2009. Long non-coding RNAs: insights and functions. Nature Reviews Genetics 10:155-159.

6. (Rand) The melanocortin receptors (mcr1-5) are found in a variety of vertebrate tissues and known to regulate a large number of physiological functions. Polymorphisms in the genes coding for these proteins influence variation in stress, skin and hair pigmentation, appetite and energy metabolism, neurological function, and immune function, to name a few. Choose one of the physiological functions of the melanocortin system and review the genetic basis for variation in this system.

Anderson, T. M., B. M. von Holdt, S. I. Candille, M. Musiani, C. Greco, D. R. Stahler, D. W. Smith, B. Padhukasahasram, E. Randi, J. A. Leonard, C. D. Bustamante, E. A. Ostrander, H. Tang, R. K. Wayne, and G. S. Barsh. 2009. Molecular and evolutionary history of melanism in North American gray wolves. Science 323:1339-1343.

Ducrest, A.L., L. Keller, and A. Roulin. 2008. Pleiotropy in the melanocortin system, coloration and behavioural syndromes. Trends in Ecology and Evolution 23:502-510.

Gao X, K. C. Simon, J. Han, M. A. Schwarzschild, and A. Ascherio. 2009. Genetic determinants of hair color and Parkinson’s disease risk. Annals of Neurology 65:76-82.

Hillebrand, J. J., M. J. Kas , and R. A. Adan. 2006. To eat or not to eat; regulation by the melanocortin system. Physiology & Behavior 89:97-102.

Mundy, N. I. 2009. Conservation and convergence of colour genetics: MC1R mutations in brown cavefish. PLoS Genetic 5:e1000388.

Skibicka, K. P., and H. J. Grill. 2009. Hindbrain leptin stimulation induces anorexia and hyperthermia mediated by hindbrain melanocortin receptors. Endocrinology 150:1705-1711.

Steiner, C. C., H. Römpler, L. M. Boettger, T. Schöneberg, and H. E. Hoekstra. 2009. The genetic basis of phenotypic convergence in beach mice: similar pigment patterns but different genes. Molecular Biology and Evolution 26:35-45.

7. (Henderson) G protein-coupled receptors (GPCRs) are the largest family of proteins encoded by the human genome. These receptors initiate second-messenger signaling cascades that are essential for many human physiological processes. Therefore, it is not surprising that mutations in the genes encoding GPCRs are the cause of many human diseases or that GPCRs are targets of about 50% of all currently approved drugs. Review the signaling pathways activated/inactivated by a particular GPCR in a human disease and suggest/discuss an alternative target for drugs aimed at the diseases caused by improperly functioning GPCRs.

Spiegel, A.M., and L. S. Weinstein. 2004. Inherited diseases involving G proteins and G protein-coupled receptors. Annual Review of Medicine 55:27-39.

Seifert, R., and K. Wenzel-Seifert. 2002. Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn-Schmiedeberg’s Archives of Pharmacology 366:381-416.

8. (McKone) Darwin’s theory of sexual selection originally emphasized the fitness benefits of multiple matings to males. However, it has also become clear that females of many species mate with multiple males (polyandry). Discuss the evolutionary causes and implications of polyandry.

Fitzpatrick, J. L., R. Montgomerie, J. K. Desjardins, K. A. Stiverbe, N. Kolmf, and S. Balshineb. 2009. Female promiscuity promotes the evolution of faster sperm in cichlid fishes. Proceedings of the National Academy of Sciences, USA 106:1128-1132.

Muller, M. N., S. M. Kahlenberg, M. E. Thompson, and R. W. Wrangham. 2007. Male coercion and the costs of promiscuous mating for female chimpanzees. Proceedings of the Royal Society of London B 274:1009-1014.

Reinhardt, K., R. A. Naylor, and M. T. Siva-Jothy. 2009. Situation exploitation: higher male mating success when female resistance is reduced by feeding. Evolution 63:29-39.

Seeley, T. D., and D. R. Tarpy. 2007. Queen promiscuity lowers disease with honeybee colonies. Proceedings of the Royal Society of London B 274:67-72.

9. (Walser-Kuntz and McKone) The human body contains an order of magnitude more microbial cells than eukaryotic cells. Many other species of animals and plants have similarly large internal microbial communities (“microbiomes”). Discuss the impact of microbiomes on the physiology, ecology, or evolution of multicellular organisms.

Dethfelsen, L., M. McFall-Ngai, and D. A. Relman. 2007. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449:811-818.

Hattori1, M., and T. D. Taylor. 2009. The human intestinal microbiome: a new frontier of human biology. DNA Research 16:1-12.

Ley, R. E., M. Hamady, C. Lozupone, P. J. Turnbaugh, R. R. Ramey, J. S. Bircher, M. L. Schlegel, T. A. Tucker, M. D. Schrenzel, R. Knight, and J. I. Gordon. 2008. Evolution of mammals and their gut microbes. Science 320:1647-1651.

Warnecke, F., et al. 2007. Megagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite. Nature 450:560-565.