Faculty available to advise comps: Hernández, Jaramillo, McKone, Rand, Tymoczko, Wolff, Zweifel

1. (Hernandez) – Herbivores play a key role in energy and nutrient flow, community composition, and trophic dynamics. Herbivore-mediated effects on ecosystems have been shown to influence productivity, nutrient cycling, invasion, and biodiversity. However, the consequences of herbivory on these ecological factors are highly variable depending on ecosystem type, feeding mode, population size, and species interactions.  Select a system or herbivore guild in which to examine the ecological and/or evolutionary response to herbivory and the community or ecosystem consequences of herbivore-mediated changes.

Hillebrand, H., D.S. Gruner, E.T. Borer, M.E.S. Bracken, E.E. Cleland, J.J. Elser, W.S. Harpole, J.T. Ngai, E.W. Seabloom, J.B. Shurin, and J.E. Smith. 2007. Consumer versus resource control of producer diversity depends on ecosystem type and producer community structure. Proceedings of the National Academy of Sciences, USA 104: 10904-10909.

Hillebrand, H., E.T. Borer, M.E.S. Bracken, B.J. Cardinale, J. Cebrian, E.E. Cleland, J.J. Elser, D.S. Gruner, W.S. Harpole, J.T. Ngai, S. Sandin, E.W. Seabloom, J.B. Shurin, J.E. Smith, and M.D. Smith. 2009. Herbivore metabolism and stoichiometry each constrain herbivory at different organizational scales across ecosystems. Ecology Letters 12: 516-527.

Futuyma, D. J., and A. A. Agrawal. 2009. Macroevolution and the biological diversity of plants and herbivores. Proceedings of the National Academy of Sciences, USA 106:18054-18061.

Schmitz, O.J. 2008. Herbivory from individuals to ecosystems. Annual Review of Ecology, Evolution, and Systamatics 39: 133-152.

2. (Jaramillo) – – Important advances are being made in our understanding of the neurobiological basis of the placebo effect.  Rather than a nuisance, the placebo effect points to an elaborate neural system with potential connections to the endocrine and immune systems.  Review our current understanding of pain processing in the central nervous system with an emphasis on the mechanisms of the placebo effect.

Pollo. A, and Benedetti, F. 2009.  The placebo response: neurobiological and clinical issues of neurological relevance. Progress in Brain Ressearch 175: 283-94.

Lui, F., Colloca, L., Duzzi, D., Anchisi, D., Benedetti, F., and Porro, C. A. 2010.

Neural bases of conditioned placebo analgesia. Pain 151: 816-24.

Colloca, L. and Benedetti, F. Placebos and painkillers: is mind as real as matter? 2005.  Nature Reviews Neuroscience 6: 545-552.

3. (McKone) –  (fall/winter only)  Over evolutionary history, some ancient lineages have retained the same morphology and ecological characteristics.  Yet over the same time other taxonomic groups have undergone rapid diversification and adaptive radiation to fill novel ecological roles. Explanations for such dramatic evolutionary diversification fall into two general types: extrinsic (successful groups are responding to novel opportunities, such as might occur on isolated islands) or intrinsic (they have evolved key innovations that allow them to be more successful than other groups).  Choose one or more cases of rapid evolutionary diversification, and compare extrinsic versus intrinsic hypotheses for the diversification.

Claramunt, S. 2010. Discovering exceptional diversifications at continental scales: the case of endemic families of Neotropical suboscine passerines. Evolution 64:2004-2019.

Jiao, Y., N.J. Wickett, S. Ayyampalayam, A.S. Chanderbali, L. Landherr, P.E. Ralph, L.P. Tomsho, Y. Hu, H. Liang, P.S. Soltis, D.E. Soltis, S.W. Clifton, S.E. Schlarbaum, S.C. Schuster, H. Ma, J. Leebens-Mack, and C.W. dePamphilis.  2011.  Ancestral polyploidy in seed plants and angiosperms.  Nature 473:97-100.

Losos, J.B. 2010. Adaptive radiation, ecological opportunity, and evolutionary determinism. American Naturalist 175:623-639.

Marshall, C. R., and J. W. Valentine. 2010. The importance of preadapted genomes in the origin of the animal bodyplans and the Cambrian explosion. Evolution 64:1189-1201.

4. (Rand) – Some social and reproductive behaviors have been shown to influence gene expression and subsequent behavior through epigenetic modifications of the chromatin.  These mechanisms alter the interactions between histone proteins and DNA; thus, significantly modifying the transcription of genes without changing nucleotide sequence.  These epigenetic influences can act transgenerationally, challenging our conceptions of gene-environment interactions.  Review the neuroendocrine mechanisms hypothesized to translate the behavioral environment to the epigenetic mechanisms that influence offspring behavior and the behavior of subsequent generations.

Crews, D.  (2010). Epigenetics, brain, behavior, and the environment. Hormones, 9:41-50.

Crews, D., A. C. Gore, T. S. Hsu, N. L. Dangleben, M. Spinetta, T. Schallert, M. D. Anway, and M.K. Skinner  (2007). Transgenerational epigenetic imprints on mate preference. Proc Natl Acad Sci, 104:5942 – 5946.

Curley, J.P., R. Mashoodh, and F.A. Champagne (2011) Epigenetics and the origin of paternal effects, Hormones & Behavior, 59: 306-314.

Keverne, E.B. and J.P. Curley (2008) Epigenetics, brain evolution and behaviour. Frontiers Neuroendocrinol, 29:398-412.

Meaney, M.J. (2010) Epigenetics and the biological definition of gene × environment interactions. Child Development, 81:41–79.

Shepard, K.N., M. Vasiliki, D. J. Toufexis and M. E. Wilson (2009) Genetic, epigenetic and environmental impact on sex differences in social behavior Physiol Behav, 97:157-170.

5. (Tymoczko) – Skeletal muscle has the ability to both respond and adapt to changing environmental stimuli, leading to metabolic and morphologic changes, which allows better adaptation to the demands of physical activity. Understanding the signal transduction pathways that regulate muscle growth and the subsequent metabolic modifications is an area of ongoing investigation. This research has the potential to be clinically significant since loss of muscle mass due to disuse, aging and pathological conditions has physiological and psychological ramifications.  Investigate the pathways that regulate muscle growth and describe how these pathways might be altered by behavior, disease or pharmacological manipulation.

Duan, C., Ren, H., and Gao, S. 2010. Insulin-like growth factors (IGF), IGF receptors. And IGF binding proteins: Roles in skeletal muscle growth and differentiation. General and comparative endocrinology.167: 344-351.

Wackerhage, H. and Ratkevicius, A. 2008. Signal transduction pathways the regulate muscle growth. Essays in Biochemistry 44: 99-108.

Otto, A., and Patel, K. 2010. Signalling and the control of muscle size. Experimental Cell Research 316: 3059-3066.

Dominique, J.-E., and Gérard, C. 2006. Myostatin regulation of muscle development: Molecular basis, natural mutations, physiopathological aspects. Experimental Cell Research 312: 2401-2414.

Dominique, J.-E., and Gérard, C. 2007. The myostatin gene: physiology and pharmacological relevance. Current Opinion in Pharmacology 7:310–315

6. (Tymoczko) –  Tumors have been known for decades to display enhanced rates of glucose uptake and glycolysis. Indeed, rapidly growing tumor cells will metabolize glucose to lactate even in the presence of oxygen, a process called aerobic glycolysis or the “Warburg effect,” after Otto Warburg, the biochemist who first noted this characteristic of cancer cells in the 1920s. In fact, tumors with a high glucose uptake are particularly aggressive, and the cancer is likely to have a poor prognosis. What selective advantage does aerobic glycolysis offer the tumor over the energetically more efficient oxidative phosphorylation?  What biochemical alterations facilitate the switch to aerobic glycolysis?

Vander Heiden, M.G., Lewis C. Cantley, L.C., and Thompson, C.B. 2009. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 324: 1029—1033.

Resendis-Antonio, O., Checa, A., and Encarnación, S. 2010. Modeling core metabolism in cancer cells: surveying the topology underlying the Warburg effect.

 PloS one 5: :e12383.

 Ferreira, L. M. R.  2010. Cancer metabolism: the Warburg effect today. Experimental and molecular pathology.  89:372-380.

7.  (Wolff) – Plasticity allows a cell to dramatically change its phenotype over the course of its lifetime.  A wide array of biological processes depend on regulation of cellular plasticity; an inappropriate loss or gain of plasticity could have implications for embryonic development, tissue growth and repair, learning and memory, or aging, for example.  Recent studies have shed light on genetic mechanisms of cellular plasticity and reprogramming, and on the therapeutic potential for experimentally manipulating cell fate. 

Discuss the role of cellular plasticity, with emphasis on cellular and molecular mechanisms, in one (or more) of the following:  

a)     Normal development and function of a tissue or organ

b)    Regeneration or repair of a diseased or damaged tissue

c)     Production and therapeutic potential of induced pluripotent stem cells (iPSCs)

d)    Cancer

e)     Aging

Suggested reading:

Puri and Hebrok. Cellular plasticity within the pancreas–lessons learned from development. Dev Cell (2010) vol. 18 (3) pp. 342-56

Mercola et al. Cardiac muscle regeneration: lessons from development. Genes Dev (2011) vol. 25 (4) pp. 299-309

Stadtfeld and Hochedlinger. Induced pluripotency: history, mechanisms, and applications. Genes Dev (2010) vol. 24 (20) pp. 2239-63

Lathia et al. Deadly teamwork: neural cancer stem cells and the tumor microenvironment. Cell Stem Cell (2011) vol. 8 (5) pp. 482-5

8.   (Zweifel) – Within a eukaryotic cell, transcription occurs in the context of chromatin.  And since chromatin is generally inhibitory to transcription, one of the key control steps required to activate transcription is a process termed chromatin remodeling.  These remodeling complexes move or displace nucleosomes from DNA and facilitate the recruitment and assembly of transcription initiation complexes.  Even during transcription elongation, nucleosomes must be removed, reassembled rapidly, and modified appropriately following passage of the RNA polymerase.  Examine the mechanism and function of chromatin remodeling, and discuss how this function allows for the rapid activation of transcription. 

Fuda, N. J., Ardehali, M.B. and J. T. Lis.  2009.  Defining mechanisms that regulate RNA polymerase II transcription in vivo.  Nature 461: 186-192.

Weake, V. M. and J. L. Workman.  2010.  Inducible gene expression: diverse regulatory mechanisms.  Nature Rev. Genet. 11: 426-437.

9.  (Zweifel) – The promise of gene-based therapy for treating human diseases has been around for over 20 years.  After intense enthusiasm  at the inception of this technology, researchers ran into serious  setbacks, including safety concerns.  However, recent advances in gene  delivery technology have sparked renewed interest in this field of  medical research.  Examine the current state of affairs of gene  therapy, and how the hurdles associated with gene-based therapy are  being tackled. Discuss the modes of gene delivery, and evaluate the  potential for success of these mechanisms.

Nature Reviews Genetics, May 2011. A series of articles focusing on  gene-based therapies.