1. Role of the extracellular matrix
Mitra (Fall/Winter & Winter/Spring)
The extracellular matrix (ECM) is a three dimensional, non-cellular structure that plays an important role in a variety of biological processes. For example, receptors for ECM proteins exert crosstalk with various growth factor and cytokine receptors. Additionally, the ECM is highly dynamic and continuously remodeled. In diseases such as cancer the ECM is deregulated and can become disorganized. Choose a biological process involving the ECM and examine the mechanisms that control this process on a cellular, molecular and biochemical level.
Bonnans, C., Chou, J., and Werb, Z. (2014). Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15, 786-801.
Brizzi, M.F., Tarone, G., and Defilippi, P. (2012). Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol 24, 645-651.
Gilkes, D.M., Semenza, G.L., and Wirtz, D. (2014). Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer14, 430-439.
Hallmann, R., Zhang, X., Di Russo, J., Li, L., Song, J., Hannocks, M.J., and Sorokin, L. (2015). The regulation of immune cell trafficking by the extracellular matrix. Curr Opin Cell Biol 36, 54-61.
Watt, F.M., and Huck, W.T. (2013). Role of the extracellular matrix in regulating stem cell fate. Nat Rev Mol Cell Biol 14, 467-473.
2. Cancer and the immune system
Walser-Kuntz (Fall/Winter only)
As early as 1890, physicians searching for alternatives to surgery as a cancer treatment turned to the immune system. Since these early, risky trials, the field of immunotherapy has grown to include monoclonal antibodies, dendritic cell vaccines, and novel combination therapies. Although we know that cells of the immune system have the potential to recognize and destroy cancer cells, in many cases the tumor evades the immune response. Explore the mechanisms involved in one of the following: immunotherapy, tumor microenvironment and immune evasion, or the recognition and destruction of cancer cells by the immune system.
Woo, S. L. Corrales, and T. Gajewski. 2015. Innate Immune Recognition of Cancer Annual Review of Immunology 33:445-474.
Vandenberk, L., J. Belmans, M. Van Woensel, M. Riva, & S. Van Gool. 2015. Exploiting the Immunogenic Potential of Cancer Cells for Improved Dendritic Cell Vaccines. Frontiers in Immunology 6:663.
Scott, A., J. Wolchok, & L. J. Old. 2012. Antibody therapy of cancer. Nature Reviews Cancer 12:278-287.
Joyce, J. & D. Fearon. 2015. T cell exclusion, immune privilege, and the tumor microenvironment. Science 348:74-80.
3. The causes and consequences of ecological regime shifts to alternate stable states
Hernandez (Fall/Winter & Winter/Spring)
McKone (Fall/Winter only)
Ecosystems constantly experience gradual changes in the abiotic and biotic components of the system. For example, changes in climate, nutrient availability, and species assembly are common occurrences over both short and long time scales. In many cases, the response to these changes is gradual as well, as communities and ecosystems processes are altered slightly by the changes in environmental conditions. However, it is also possible for communities and ecosystems to undergo sudden and dramatic shifts in response to changing conditions, creating a “regime shift” to an alternate stable state. For this question, consider the causes and consequences of ecological regime shifts at the community and/or ecosystem level.
Brandt, J. S., M. A. Haynes, T. Kuemmerle, D. M. Waller, V. C. Radeloff. 2013. Regime shift on the roof of the world: Alpine meadows converting to shrublands
in the southern Himalayas. Biological Conservation 158:116-127.
Graham, N. A. J., S. Jennings, M. A. MacNeil, D. Mouillot, and S. K. Wilson. 2015. Predicting climate-driven regime shifts versus rebound potential in coral reefs. Nature 518:94-97.
Isbell, F., D. Tilman, S. Polasky, S. Binder, and P. Hawthorne. 2013. Low biodiversity state persists two decades after cessation of nutrient enrichment. Ecology Letters 16:454-460.
Scheffer, M., S. Carpenter, J.A. Foley, C. Folke, and B. Walker. 2001. Catastrophic shifts in ecosystems. Nature 413:591-596.
Schooler, S. S., B. Salau, M. H. Julien, and A. R. Ives. 2011. Alternative stable states explain unpredictable biological control of Salvinia molesta in Kakadu. Nature 470:86-89.
Staver, A. C., S. Archibald, and S. Levin. 2011. Tree cover in sub-Saharan Africa: rainfall and fire constrain forest and savanna as alternative stable states. Ecology 92(5):1063-1072.
4. Evolutionary responses to the Anthropocene
McKone (Fall/Winter only)
Hougen-Eitzman (Winter/Spring only)
The dramatic and myriad global changes caused by human domination of our planet have prompted designation of our era as the Anthropocene. The evolutionary trajectories of many species have changed as they adapt to this new world. Review the nature and rate of evolutionary changes in response to human modification of the Earth. Possible topics include adaptation to novel environments, such as urban or agricultural landscapes; or adaptation to human-mediated losses of species or introductions of non-native species.
Belgrano, A., and C.W. Fowler. 2013. How fisheries affect evolution. Science 342:1176-1177.
Donihue, C.M., and M.R. Lambert. 2015. Adaptive evolution in urban ecosystems. AMBIO 44:194-203.
Fletcher, R.A., R.M. Callaway, and D.Z Atwater. 2016. An exotic invasive plant selects for increased competitive tolerance, but not competitive suppression, in a native grass. Oecologia 181:4999-505.
Waselkov, K.E., and K.M. Olsen. 2014. Population genetics and origin of the native North American agricultural weed waterhemp (Amaranthus tuberculatus; Amaranthaceae). American Journal of Botany 101:1726-1736.
5. Epigenetic influences on behavior
Zweifel (Fall/Winter & Winter/Spring)
Environmental influence on gene expression and behavior has ushered in the fascinating field of behavioral epigenetics. Noncoding RNA, DNA methylation, and histone modification are the three horsemen often associated with epigenetic control of gene expression. Understanding epigenetic influence on behavior may help lead to progress in treatments of conditions such as substance abuse, schizophrenia, autism, and a host of other behavioral conditions. From animal models to human medical conditions, researchers are using genome-based analysis of epigenetics to shed new light on the complex interaction of genes and environment. Examine the molecular techniques and experimental results that are elucidating the epigenetic regulation of behavior.
Powledge, T. M. (2011). Behavioral epigenetics: how nurture shapes nature. Bioscience 61, 588-592.
The following web site from Nature highlights a number of current articles in “Epigenetics and Behavior”: http://www.nature.com/subjects/epigenetics-and-behaviour
6. Altered metabolism in cancer cells
Broege (Fall/Winter & Winter/Spring)
Somatic cells under normoxic conditions generate energy through oxidative phosphorylation. Cancer cells, however, undergo a metabolic shift from oxidative phosphorylation as their primary means of generating energy to aerobic glycolysis. During aerobic glycolysis, pyruvate generated from glycolysis is fermented to lactate even in the presence of oxygen. This metabolic switch in cancer cells was identified by Otto Warburg in the 1920s and named the Warburg effect. Recent studies have explored the central role that metabolic changes in cancer cells – not limited to changes in glucose metabolism – play during tumor progression. Understanding the cellular changes that lead to altered metabolism in cancer has identified new targets for cancer therapeutics. For this question, explore an example of altered metabolism in the context of cancer and elaborate upon cellular mechanisms that facilitate this shift.
Ward, P.S., and Thompson, C.B. 2012. Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate. Cancer Cell 21: 297-308.
Carracedo, A., Cantley, L.C., and Pandolfi, P.P. 2013. Cancer metabolism: fatty acid oxidation in this limelight. Nature Reviews Cancer 13: 227-232.
Schulze, A. and Harris, A.L. 2012. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 491: 365-373.
Flaveny, C.A., Griffett, K., et al. 2015. Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis. Cancer Cell 28, 42-56.
Nieman K.M., Kenny H.A., et al. 2011. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nature Medicine 17 (11), 1498-1503.
7. Evo-devo and animal diversity
Wolff (Fall/Winter & Winter/Spring)
Diversity among animals has arisen as a result of evolutionary forces acting on phenotypic variation caused by changes in developmentally expressed genes. Often these changes affect the timing, amount, or location of gene expression or function rather than resulting from the acquisition or loss of genes. Describe the role of differential gene expression or function in the development and evolution of an animal body plan, structure, or other phenotype.
Agaba, M., Ishengoma, E., Miller, W.C., McGrath, B.C., Hudson, C.N., Reina, O.C.B., Ratan, A., Burhans, R., Chikhi, R., Medvedev, P., et al. (2016). Giraffe genome sequence reveals clues to its unique morphology and physiology. Nature Communications 7, 1–8.
Carroll, S.B. (2006). Endless Forms Most Beautiful: The New Science of Evo Devo (W. W. Norton & Company).
Ito, F., Takeda, H., Yano, T., Okabe, M., Kuraku, S., Keeley, F.W., Moriyama, Y., and Koshiba-Takeuchi, K. (2016). Evolution of the fish heart by sub/neofunctionalization of an elastin gene. Nature Communications 7, 1–10.
Gehrke, A.R., and Shubin, N.H. (2016). Cis-regulatory programs in the development and evolution of vertebrate paired appendages. Seminars in Cell and Developmental Biology 1–9.
Gilbert, S.F., Bosch, T.C.G., and Ledón-Rettig, C. (2015). Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents. Nat Rev Genet 16, 611–622.
Gilles, A.F., and Averof, M. (2014). Functional genetics for all: engineered nucleases, CRISPR and the gene editing revolution. Evodevo 5, 43.
Levine, M. (2010). Transcriptional Enhancers in Animal Development and Evolution. Curr Biol 20, R754–R763.
Pereira, J., Johnson, W.E., O’Brien, S.J., Jarvis, E.D., Zhang, G., Gilbert, M.T.P., Vasconcelos, V., and Antunes, A. (2014). Evolutionary Genomics and Adaptive Evolution of the Hedgehog Gene Family (Shh, Ihh and Dhh) in Vertebrates. PLoS ONE 9, e74132.