Department of Biology Integrative Exercise Questions: 2012–2013

1) David Hougen-Eitzman: Most ecosystems are nutrient-limited, and nutrient levels (such as N and P) usually have strong effects on species diversity, productivity, and ecosystem function.  However, as human population levels increase, with a concomitant rise in standard of living, many ecosystems are experiencing nutrient loading beyond historically normal levels.  Now, nutrients that were in low supply are now abundant – this novel situation can cause broad changes in natural systems.  Focusing on one type of ecosystem, examine how nutrient loading affects ecosystem and/or community properties.

Abell, J.M., Ozkundakci, D., and Hamilton, D.P. (2010). Nitrogen and Phosphorus Limitation of Phytoplankton Growth in New Zealand Lakes: Implications for Eutrophication Control. Ecosystems 13, 966-977.

Cusack, D.F., Silver, W.L., Torn, M.S., Burton, S.D., and Firestone, M.K. (2011). Changes in microbial community characteristics and soil organic matter with nitrogen additions in two tropical forests. Ecology 92, 621-632.

Howarth, R., Chan, F., Conley, D.J., Garnier, J., Doney, S.C., Marino, R., and Billen, G. (2011). Coupled biogeochemical cycles: eutrophication and hypoxia in temperate estuaries and coastal marine ecosystems. Front. Ecol. Environ. 9, 18-26.

Penuelas, J., Sardans, J., Rivas-Ubach, A., and Janssens, I.A. (2012). The human-induced imbalance between C, N and P in Earth’s life system. Glob. Change Biol. 18, 3-6.

Phoenix, G.K., Emmett, B.A., Britton, A.J., Caporn, S.J.M., Dise, N.B., Helliwell, R., Jones, L., Leake, J.R., Leith, I.D., Sheppard, L.J., et al. (2012). Impacts of atmospheric nitrogen deposition: responses of multiple plant and soil parameters across contrasting ecosystems in long-term field experiments. Glob. Change Biol. 18, 1197-1215.

2) Mark McKone: Sex chromosomes (such as X/Y in mammal or Z/W in birds) have evolved multiple times in diverse lineages of animals and plants.  The two sex chromosomes differ from each other and from the autosomes in many fascinating ways.  Discuss the origin of sex chromosomes, and the consequences for subsequent evolutionary events once they have arisen in a lineage.

Bellott, D.W., Skaletsky, H., Pyntikova, T., Mardis, E.R., Graves, T., Kremitzki, C., Brown, L.G., Rozen, S., Warren, W.C., Wilson, R.K., and Page, D.C. (2010). Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition.  Nature 466, :612-616.

Ellegren, H. (2011). Sex-chromosome evolution: recent progress and the influence of male and female heterogamety. Nature Reviews Genetics 12, 157-166.

Mank, J. E., Hosken, D.J, and Wedell, N. (2011). Some inconvenient truths about sex chromosome dosage compensation and the potential role of sexual conflict. Evolution 65, :2133-2144.

3) Mark McKone: Life on Earth experienced profound changes between 10 and 20 thousand years ago.  First, this was a period of glaciation that dramatically shifted the global distribution of many ecological communities.  Second, most of the largest land animals (“megafauna”) became extinct in North America and other large land masses.  Consider the impact of glaciation or of megafaunal extinction on the ecological characteristics of species and communities today.

Guimarães, P. R., Jr., Galetti, M. and Jordano, P.. (2008). Seed dispersal anachronisms: rethinking the fruits extinct megafauna ate. PLoS ONE 3, e1745.

Rule, S., B. W. Brook, S. G. Haberle, C. S. M. Turney, A. P. Kershaw, and C. N. Johnson. 2012. The aftermath of megafaunal extinction: ecosystem transformation in Pleistocene Australia. Science 335, 1483-1486.

Sandel, B., Arge, L., Dalsgaard, B., Davies, R.G., Gaston, K.J., Sutherland, W.J., and Svenning, J.C. (2011). The influence of Late Quaternary climate-change velocity on species endemism. Science 334, 660-664.

Shafer, A. B. A., Côté, S.D., and Coltman, D.W. (2011). Hot spots of genetic diversity descended from multiple Pleistocene refugia in an alpine ungulate. Evolution 65, 125-138.

4) Raka Mitra: Vascular plants are dead on the inside.  The xylem, which carries water and solutes through the plant, is made up of tracheary elements, which were once live cells that underwent a unique form of programmed cell death.  Review our current understanding of xylem development, and explore how living plant cells can regulate an essential process within the xylem, such as the control of water flow, pathogen defense or signal molecule transport.

Ye, Z.H , (2002). Vascular tissue differentiation and pattern formation in plants. Annu. Rev.

Plant Biol. 53, 183-202.

Lehesranta, S.J., Lichtenberger, R., and Helariutta. Y. (2010). Cell-to-cell communication in

vascular morphogenesis. Curr. Opin. Plant Biol. 13, 59-65.

5) Raka Mitra:  The recent identification of nucleases that can be engineered to target specific DNA sequences has been hailed as a promising development in genetic engineering.  There are three major classes of these nucleases: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and engineered meganucleases.  Identification and characterization of all three types of nucleases came out of basic research studies on DNA repair, restriction nucleases and DNA binding proteins.  Engineered nucleases can be used to modify the genome in a variety of ways and have allowed scientists to investigate new avenues of research.  For example, a ZFN-based approach has been developed for the treatment of glioblastoma and HIV.  Additionally, nucleases can be used to create transgenic animals that function as better model systems for human disease and physiology.  Choose one of the classes of nucleases, review the fundamental work that led to their understanding and explore how this type of nuclease can be used to tackle a biological problem that has thus far been intractable.

de Souza, N . (2012). Primer: genome editing with engineered nucleases. Nature Methods 9, 27.

Baker, M. (2012 ). Gene-editing nucleases. Nature Methods 9, 23–26.

6) Amy Moore: Epidemiologists traditionally report disease rates in males and females.  Yet only recently have research and public health initiatives recognized that genetic- or hormonally-based sex differences might impact disease etiology, progression and response to therapy.  Identify a disease that displays sex-bias and describe biological factors that account for the sex-bias.

McCarthy, M, Arnold, A P, Ball, G F, et al. (2012). Sex differences in the brain: The not so inconvenient truth. The Journal of neuroscience, 32, 2241-2247.

Frick, K M. (2012). Building a better hormone therapy? how understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline. Behavioral neuroscience, 126, 29-53.

Klein, S L. (2012). Immune cells have sex and so should journal articles. Endocrinology,  Mar 20 [epub ahead of print]

Hilliard, L M, Nematbakhsh, M, Kett, M, et al. (2011). Gender differences in pressure-natriuresis and renal autoregulation: Role of the angiotensin type 2 receptor. Hypertension, 57, 275-282.

Arnold, A P, and & Lusis, A J. (2012). Understanding the sexome: Measuring and reporting sex differences in gene systems. Endocrinology, Mar 20 [epub ahead of print]

Shen, N, Fu, Q, Deng, Y, et al. (2010). Sex-specific association of x-linked toll-like receptor 7 (tlr7) with male systemic lupus erythematosus. Proc. Nat. Acad. Sci. (U.S.A.), 107, 15838-15843.

7) John Tymoczko:  Proteins synthesized in the endoplasmic reticulum (ER) fold with the assistance of ER chaperone proteins. When misfolding occurs, proteins are degraded by ER-associated protein degradation (ERAD). If the amount of unfolded protein exceeds the folding capacity of the ER, cells activate a defense mechanism called the ER stress response, which inhibits most protein synthesis but induces expression of ER chaperones and ERAD components in order to degrade the defective proteins. A malfunction of the ER stress response has been implicated in various diseases including diabetes, inflammation, and neurodegenerative disorders including Alzheimer’s disease, and Parkinson’s disease.

Describe the molecular underpinnings of the unfolded protein response and review its role in the development of pathological conditions.

Ozcan, L. and Tabas, I. (2012) Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu. Rev. Med. 63, 317–328.

Meusser, B., Hirsch, C., Jarosch, E., and Sommer, T. (2005). ERAD: The long road to destruction. Nature Cell Biol. 7, 766-772.

Deldicque, L., Hespel, P., and Francaux, M. (2012). Endoplasmic Reticulum Stress in Skeletal Muscle: Origin and Metabolic Consequences. Exerc. Sport Sci. Rev. 40, 43-49.

8) John Tymoczko: Brown adipose tissue (BAT) is recognized to have an important role in the maintenance of body temperature in animals including human babies and adults. There are suggestions that that BAT activity might also play a role in regulating fat storage and the development of obesity. Exercise has recently been shown to increase the amount of BAT.

How does brown adipose tissue develop and function? What is its role beyond thermogenesis? What mechanism account for differences in BAT activity with age, gender, body mass index or exercise level?

Ravussin E.,  and José E. Galgani, J.E. (2011). The implication of brown adipose tissue for humans. Annu. Rev. Nutr. 31, 33-47.

Bostrom, P., Wu, J., Jedrychowski, M.P., Korde, A., Ye, L. et al. (2012). A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463-468.

Cypess, A. M., Sanaz Lehman, S., Gethin Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A.,  Kolodny, G. M., and Kahn, C. R. (2009). Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509–1517.

Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., and Nuutila, P. (2009). Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 360, 1518–1525.

9) Debby Walser-Kuntz:  Several virus families, including herpes-, arbo-, coxsackie-, echo-rhabdo-, and enteroviruses, may infect the central nervous system. There must be a delicate balance between protection of the host from viral invaders and immune system initiated damage to the host, including neuron death. The central nervous system (CNS) was long considered an “immune privileged” site due to the blood brain barrier and limited lymphatic drainage – but this view is changing. Explore our current understanding of the antiviral immune responses which occur in the CNS.

Wilson, E., Weninger, W., and Hunter, C (2010). Trafficking of immune cells in the central nervous system. J. Clin. Invest.120, 1368–1379.

Hanke,  M, and Kielian, T.(2011).. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond)., 121, 367-87.

Chevalier,G., , Suberbielle, E., et al.(2011).. Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection. PLoS Pathog. 7, e1002393. doi:10.1371/journal.ppat.1002393.

10) Jennifer Wolff: The adage that “Timing is everything” is particularly true in biology.  Biological clocks govern processes including embryonic patterning, developmental timing, circadian rhythm, cell cycle control, and reproductive cycle, ensuring that events occur on schedule.  The molecular oscillators and timekeepers that make up these biological clocks are thus critical for viability, behavior, fertility, productivity, and health in plants and animals (including humans).  Choose a process for which a biological clock is important, and explore its genetic and molecular basis.

Ambros, V. (2011). MicroRNAs and developmental timing. Curr. Opin. Genet. Dev. 21, 511-517.

McClung, C.R and Gutiérrez, R.A. (2010). Network news: prime time for systems biology of the plant circadian clock. Curr. Opin. Genet. Dev. 20, 588-98.

Mohawk, J.A, Green, C.B, and Takahashi, J.S. (2012). Central and Peripheral Circadian Clocks in Mammals. Annu. Rev. Neuro. 2012, epub ahead of print.

Oates, A.C, Morelli, L.G, and Ares, S. (2012). Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock. Development 139, 625-639.

Poethig, R.S.  (2009). Small RNAs and developmental timing in plants. Curr. Opin. Genet. Dev. 19, 374-378.

Rando, T.A,  and Chang, H.Y.  (2012). Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell 148, 46-57.

Sehgal, A,  and Mignot, E. (2011) Genetics of sleep and sleep disorders. Cell 146, 194-207.