INTEGRATIVE EXERCISE QUESTIONS 2005-06
FACULTY AVAILABLE TO CHAIR COMPS COMMITTEES: Camill (fall accelerated or fall/spring only), Hougen-Eitzman, McKone, Reinke, Rosenberg, Singer (fall accelerated and fall/winter only), Tymoczko, Walser-Kuntz, and Zweifel
1. (Zweifel, Reinke) In eukaryotes, small RNA molecules engage in sequence-specific interactions to inhibit gene expression. This process, known as RNA silencing or RNA interference (RNAi), contributes to diverse expression patterns and may regulate various developmental and physiological processes. Our understanding of the regulation of gene expression and complex gene regulatory networks has been revolutionized by the discovery of microRNAs and small interfering RNAs. RNAi regulates gene expression in organisms from yeast to humans through processes as diverse as RNA degradation and epigenetic modification. (1) In addition to regulating gene expression, RNA silencing in plants and insects provides a source of cellular defense against viruses. In turn, viral pathogens have evolved strategies that allow them to evade the host silencing machinery. Examine the mechanism of RNA silencing and the role it may have in gene regulation and antiviral defense, or (2) Review our current understanding of the mechanism of RNAi, focusing on the mechanistic differences among different organisms and the biological consequences of this diversity, or (3) Review our current understanding of the mechanism of RNAi as an experimental technique and a therapeutic agent, focusing on the advantages and limitations of its use in genetic investigations, drug discovery and disease therapy.
Llave, C. 2004. MicroRNAs: more than a role in plant development? Mol. Plant Pathol. 5:361-366.
He, L. and G. Hannon. 2004. MicroRNAs: small RNAs with a big role in gene regulation. Nature Rev. Genetics 5: 522-531.
Mello, C.C., D. Conte, Jr. 2004. Revealing the world of RNA interference. Nature 431:338-42.
Hannon, G.J., J.J. Rossi. 2004. Unlocking the potential of the human genome with RNA interference. Nature 431:371-8.
Tomari, Y, P.D. Zamore. 2005. Perspective: machines for RNAi. Genes Dev. 19(5):517-29.
O'neill, M.J. 2005. The influence of non-coding RNAs on allele-specific gene expression in mammals. Hum Mol Genet. 14 Suppl 1:R113-20.
2. (Walser-Kuntz) Viruses have evolved mechanisms to manipulate and subvert the host immune response. Examples include the down regulation of MHC molecules by cytomegalovirus, manipulation of apoptosis by the tat protein of HIV, production of cytokine mimics by Epstein Barr virus, and inhibition of natural killer cells by the hepatitis C virus. Describe the mechanisms used by a particular virus to successfully evade the host immune response.
Benedict, C., P. Norris, & C. Ware. 2002. To kill or be killed: viral evasion of apoptosis. Nature Immunology 3: 1013–1018. doi:10.1038/ni1102-1013
Orange, J., M Fassett, L Koopman, J Boyson & J Strominger. 2002. Viral evasion of natural killer cells. Nature Immunology 3: 1006–1012. doi:10.1038/ni1102-1006
3. (Tymoczko) Humans have consumed alcohol, in some form or another, foe millennia. Indeed, before the ready accessibility of pure water, alcoholic beverages may have been a prime source to meet hydration needs. However, it is only in recent years that studies have been undertaken to detail the biochemical effects of alcohol. The liver is the primary site of alcohol metabolism. Examine (1) how ethanol is metabolized by the liver and the effects of this metabolism on the liver specifically and the organism as a whole or (2) the biochemical basis for behavioral responses to ethanol and the mechanisms underlying ethanol-related neurological disease.
Nagy, L.E. 2004. Molecular Aspects of Alcohol Metabolism: Transcription Factors Involved in Early Ethanol-Induced Liver Injury. Annual Reviews of Nutrition 24:55-78.
M. You, and D. W. Crabb. 2004. Recent Advances in Alcoholic Liver Disease II. Minireview: molecular mechanisms of alcoholic fatty liver Am J Physiol Gastrointest Liver Physiol, 287: G1 - G6.
Ron, D. 2004. Signaling Cascades Regulating NMDA Receptor Sensitivity to Ethanol Neuroscientist, 10: 325 - 336.
4. (Tymoczko) The average age of citizens of the developed world is rising rapidly. Despite the fact that aging is among the most familiar of biological processes, it remains poorly understood. This is true in part because of the variability of the factors that affect the process, which include factors such as caloric intake, genetic makeup, stress, hormones and infection. In recent years, the scientific community has begun a major effort to understand this process. Review and evaluate some of the theories of aging.
Reviews on Aging. Cell Volume 4, Number 4 (the entire issue), 2004
5. (Walser-Kuntz, Hougen-Eitzman) Malaria is a disease that involves three organisms in a highly coevolved system -- parasite, mosquito, and human. Successful transmission from one human to another requires that the parasite evade the immune systems of both mosquito and humans. Please address one of the following questions: How do the parasites circumvent immune response in mosquitoes and/or humans? Can malaria be effectively controlled by focusing on the mosquito vector? Why are vaccines currently ineffective?
Bond, J., J. C. Rojas, J. I. Arredondo-Jimenez, H. Quiroz-Martinez, J. Valle, and T. Williams. 2004. Population control of the malaria vector Anopheles pseudopunctipennis by habitat manipulation. Proceedings of the Royal Society of London, Series B: Biological Sciences 271:2161-2169.
Dimopoulos, G. 2003. Insect immunity and its implication in mosquito-malaria interactions. Cellular Microbiology 5:3-14.
Miller, L. and B. Greenwood. 2002. Malaria--a Shadow over Africa. Science 298:121-122.
Mueller, A, M. Labaied, S. Kappe, and K. Matuschewski. 2005. Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature 433:164-167.
6. (Singer, Reinke) One of the key events in developmental biology is establishing polarity, exemplified by shoot-root axis establishment in plants and the anterior-posterior and dorsal-ventral axes in some animals. Focusing on either plants or animals, evaluate the current literature and propose a mechanistic model for how this polarity is established.
Laux, T., T. Würschum, and H. Breuninger. 2004. Genetic Regulation of Embryonic Pattern Formation. Plant Cell 16:S190-S202.
R. Lyczak, Gomes, J.E., Bowerman , B. 2002. Heads or tails: cell polarity and axis formation in the early Caenorhabditis elegans embryo. Dev Cell. 2:157-66. Review.
M. Zernicka-Goetz. 2004. First cell fate decisions and spatial patterning in the early mouse embryo. Semin Cell Dev Biol. 5:563-72. Review.
H. Meinhardt. 2004. Models for the generation of the embryonic body axes: ontogenetic and evolutionary aspects. Curr Opin Genet Dev. 4:446-54. Review.
7. (Singer) Pollination in plants is regulated through a unique cell-cell recognition mechanisms. Self-self recognition leads to the rejection of pollination while in other self recognition models we are aware of (e.g. our own immune system), self-nonself recognition leads to a rejection mechanism. Explore the role of self-self recognition in flowering plants and propose a model for how self-self recognition prevents pollination between closely related individuals.
Kachroo, A., M.E. Nasrallah, and J. B. Nasrallah. 2002. Self-Incompatibility in the Brassicaceae: Receptor–Ligand Signaling and Cell-to-Cell Communication Plant Cell 14: S227-S238.
Kao, T. and T. Tsukamoto. 2004. The Molecular and Genetic Bases of S-RNase-Based Self-Incompatibility Plant Cell 16: S72-S83.
8. (Camill) Nutrient pollution in coastal waters has the potential to impact estuaries and coral reefs by altering carbon cycling (productivity and decomposition), autotrophy vs. heterotrophy, element ratios, species abundance, and microbial processes. Also, additional site-specific factors, including disturbances, disease, seasonality, and hydrology, often make the nutrient loading story challenging to generalize. Evaluate how anthropogenic additions of nutrients can lead to changes in a coastal marine ecosystem.
Downing, J.A., et al. 1999. Meta-analysis of marine nutrient-enrichment experiments: variation in the magnitude of nutrient limitation. Ecology 80 4:1157.
Slomp, C.P., P. Van Cappellen. 2004. Nutrient inputs to the coastal ocean through submarine groundwater discharge: controls and potential impact. Journal of Hydrology 295 1-4: 64-86.
Smith, V.H. 2003. Eutrophication of freshwater and coastal marine ecosystems - A global problem. Environmental Science and Pollution Research 10 2:126-139.
Conley, D.J. 1999. Biogeochemical nutrient cycles and nutrient management strategies. Hydrobiologia 410: 87-96.
Herbert, R.A. 1999. Nitrogen cycling in coastal marine ecosystems. FEMS Microbiology Reviews 23 (5): 563-590.
9. (Reinke) The intracellular destruction of proteins by means of the ubiquitin-proteasome pathway is a highly regulated phenomenon that is as essential to life as protein synthesis. The ubiquitin-proteasome pathway influences diverse cellular processes such as cell cycle progression, signal transduction and transcriptional regulation. In addition, aberrations in ubiquitin-proteasome mediated proteolysis underlie the pathogenesis of many human diseases. Review the molecular mechanisms of ubiquitin-proteasome proteolysis as they relate to cellular homeostasis, and consider the pathological effects of pathway disruption at the cellular and organismal level.
Ciechanover, A. 2005. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol. 1:79-87.
Yamasaki , L, M. Pagano. 2004. Cell cycle, proteolysis and cancer. Curr Opin Cell Biol. 6:623-8. Review.
Goldberg, A.L. 2003. Protein degradation and protection against misfolded or damaged proteins. Nature. 426 6968:895-9. Review.
10. (McKone) As the number of fully sequenced genomes has accumulated, there has been increasing interest in the evolutionary forces that shape the size and makeup of genomes. In particular, the amount of DNA within a genome is influenced by a variety of processes that operate on different scales, such as (1) the gain and loss of introns within individual genes, (2) the duplication and deletion of genes, and (3) the occasional duplication of the entire genome, with subsequent loss of large fractions of the doubled genome. Discuss how extant genomes have been influenced by one (or more) of these processes of DNA gain and loss.
Kellis, M., B.,W. Birren, and E.S. Lander. 2004. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cereviseae. Nature 428:617-624.
Roy, S.W., and W. Gilbert. 2005. Rates of intron loss and gain: implications for early eukaryotic evolution. PNAS 102:5773-5778.
Zhang, J. 2003. Evolution by gene duplication: an update. Trends in Ecology and Evolution 18:292-298.
11. (McKone) Human land uses have modified landscapes throughout the world, and many large areas of once-continuous habitat have been fragmented into scattered remnants. There are many ecological and evolutionary consequences of habitat fragmentation. Review the nature of fragmentation effects at either the population, community, or ecosystem level; discuss the implication of fragmentation for long-term persistence of biological diversity.
Coulon, A., J.F. Cosson, J. M. Angibault, B. Cargnelutti, M. Galan, N. Morellet, E. Petit, S. Aulagnier, and A.J. Hewison, 2004. Landscape connectivity influences gene flow in a roe deer population inhabiting a fragmented landscape: an individual-based approach. Molecular Ecology 13: 2841-2850.
Lens, L., S. Van Dongen, K. Norris, M. Githiru, and E. Matthysen. 2002. Avian persistence in fragmented rainforest. Science 298:1236-1238.
McEuen, A.B., and L.M. Curran. 2004. Seed dispersal and recruitment limitation across spatial scales in temperate forest fragments. Ecology 85:507-518.
Tscharntke, T., I. Steffan-Dewenter, A. Kruess, and C. Thies. 2002. Characteristics of insect populations on habitat fragments: a mini review. Ecological Research 17:229-239.
12. (Rosenberg) What happens when we learn? The formation of memory must be accompanied by changes in the structure and/or function of neurons in the brain. Long-lasting changes in synaptic strength, called “long-term potentiation” and “long-term depression” (LTP and LTD), are cellular models for learning and memory. Review the pre- and post-synaptic mechanisms of LTP and LTD and discuss their strengths and weaknesses as models for learning and memory
Malenka, R.C. and M. Bear. 2004. LTP and LTD: An embarrassment of riches. Neuron 44:5-21.
Kelleher, R.J. 3rd, A. Govindarajan and S. Tonegawa. 2004. Translational regulatory mechanisms in persistent forms of synaptic plasticity. Neuron 44:59-73.
Xia, Z and D.R. Storm. 2005. The role of calmodulin as a signal integrator for synaptic plasticity. Nat. Rev Neurosci. 6:267-276.
13. (Rosenberg) Cystic fibrosis (CF) is a genetic disease in which impaired ion transport in the pulmonary epithelium leads to a thickened mucus, airway obstruction, opportunistic bacterial infection, and early death. The most common genetic causes of CF are mutations in an epithelial chloride channel, the cystic fibrosis transmembrane regulator (CFTR). But abnormal transport of ions other than chloride also plays an important role in the development of CF. Review the current literature on the cellular mechanisms of CF and discuss the multiple ionic abnormalities in the disease state.
Boucher, R.C. 2004. New concepts of the pathogenesis of cystic fibrosis lung disease. Eur. Respir. J. 23:146-158.
Guggino, W.B. and S.P. Banks-Schlegel. 2004. Macromolecular interactions and ion transport in cystic fibrosis. Am. J. Respir. Crit. Care. Med. 170:815-820.
Riordan, J.R. 2005. Assembly of functional CFTR chloride channels. Ann. Rev Physiol. 67:701-718.