2019–20 Comps Questions

1. The role of ion channels in microglial function (Fernán Jaramillo)

Recommended courses: Neurobiology (BIOL 386), Cell Biology (BIOL 280) or Immunology (BIOL 310)

Microglia, which surveil the central nervous system, have become much better understood over the last decade, as we have gradually documented the role of receptor and ion channel function in their operation. Review our current understanding of ion channel function in microglia, especially in the context of microglia’s neuro-protective functions.

Boucsein C. et al. Purinergic receptors on microglial cells: functional expression in acute brain slices and modulation of microglial activation in vitro. Eur. J. Neurosci. 2003; 17: 2267-2276.

Madry C. et al. Microglial ramification, surveillance, and interleukin-1β release are regulated by the two-pore domain K+ channel THIK-1. Neuron. 2018; 97: 299-312.

Schilling T. Eder C. Microglial K+ channel expression in young adult and aged mice. Glia. 2015; 63: 664-672. 

2. Role of Predation (David Hougen-Eitzman)

Predation (broadly defined to include parasitism and infection by pathogens) is a central organizing force in many biological systems.  Predators can be powerful actors that affect species population size and distribution, trophic dynamics, and natural selection. In the system of your choice, review the ecological or evolutionary effects of predation.  

Recommended courses: Population Ecology (Bio 352), Ecosystem Ecology (Bio 321), Agroecology (Bio 215), or Evolution (Bio 350)

Buck, J.C., Weinstein, S. B., and Young, H.S.  2018. Ecological and evolutionary consequences of parasite avoidance.  Trends in Ecology and Evolution 33:619-632.

Gaynor, K.M., Brown, J.S., Middleton, A.D., Power, M.E., and Brashares, J.S.  2019. Landscapes of fear: spatial patterns of risk perception and response. Trends in Ecology and Evolution 34:355-368.

Tomasetto, F., Tylianakis, J.M., Reale, M., Wratten, S., and Goldson, S.L.  2017. Intensified agriculture favors evolved resistance to biological control.  Proceedings of the National Academy of Sciences. 114:3885-3890

Zhang, J. Qian, H., Girardello, M., Pellissier, V., Nielsen, S.E., and Svenning, J.C. 2018.  Trophic interactions among vertebrate guilds and plants shape global patterns in species diversity.  Proceedings of the Royal Society B-Biological Sciences 285:20180949

3. Non-canonical roles of RNA (Rou-Jia Sung)

In the central dogma, RNA is typically relegated to the “intermediary” role between DNA and protein. However, RNA is an incredibly dynamic and extraordinary biological macromolecule, capable of adopting complex three-dimensional shapes that allow it to access a variety of biological functions far beyond its canonical role as temporary information storage. These functions range from catalysis (ribozymes) to regulation (riboswitches, noncoding RNAs, circular RNAs) and epitranscriptomics (chemical modifications to RNA)!

For this question, explore a non-canonical role of RNA and consider the molecular mechanism(s) and outcomes (at both the cellular and organismal level) that can result from this novel functionality.

Recommended courses: BIOL 380 or CHEM 320 or BIOL 280

Li, X, et al. 2018. The biogenesis, functions, and challenges of circular RNAs. Molecular Cell, 71: 428-442.

Roundtree, IA, et al. 2017. Dynamic RNA modifications in gene expression regulation. Cell, 169: 1187-1200.

Breaker, RR. 2018. Riboswitches and translation control. Cold Spring Harbor Perspectives in Biology, 1-14.

Topp, S and Gallivan, JP. 2010. Emerging applications of riboswitches in chemical biology. ACS Chemical Biology, 5 (1): 139-148.

4. Bacterial cells (Raka Mitra)

The field of cell biology has historically underestimated numerous aspects of bacterial cells. While eukaryotic cells were known to have membrane bound organelles, cytoskeletal proteins and innate immune pathways, these features were typically understudied in bacteria. Now, we know that bacteria make vesicles to transport materials between membranes. We know that bacteria employ proteins that are similar to eukaryotic actin and tubulin. We understand that bacteria have defense systems, such as CRISPR, in order to protect themselves against viruses.

Choose a system that has been understudied in bacterial cells explore the mechanisms that control this process on a cellular, molecular and biochemical level. Contrast this system to well-known eukaryotic systems in order to reveal surprises and new insights to be gained by studying the bacterial counterparts.

Recommended courses: Cell Biology (BIO280) and/or Microbiology (BIOL234)

Hille, F., Richter, H., Wong, S.P., Bratovic, M., Ressel, S., and Charpentier, E. (2018). The Biology of CRISPR-Cas: Backward and Forward. Cell 172, 1239-1259.

Toyofuku, M., Nomura, N., and Eberl, L. (2019). Types and origins of bacterial membrane vesicles. Nat Rev Microbiol 17, 13-24.

Wagstaff, J., and Lowe, J. (2018). Prokaryotic cytoskeletons: protein filaments organizing small cells. Nat Rev Microbiol 16, 187-201. 

5. Life in air or water (Mike Nishizaki) [DHE will also advise this question]

For organisms living in any environment, life is spent immersed in a fluid, either air or water. Not surprisingly, many biological processes are intimately tied to the behavior of those fluids (i.e., patterns of flow). For instance, the fluid environment serves as an important medium that facilitates dispersal (e.g., pollen, larvae), transports nutrients and gases (e.g., photosynthesis, respiration, calcification), and imposes physical forces affecting the shape, size, and behavior of organisms. Examine how adaptations to flow are linked to the manner in which organisms respond to environmental change, including climate change.

Recommended courses: Physiological Ecology, Population Ecology, and/or Environmental Animal Physiology

Cummins, C., Seale, M., Macente, A., Certini, D., Mastropaolo, E., Viola, I. M., & Nakayama, N. (2018). A separated vortex ring underlies the flight of the dandelion. Nature, 562(7727), 414.

Gaylord, B., Hodin, J., & Ferner, M. C. (2013). Turbulent shear spurs settlement in larval sea urchins. Proceedings of the National Academy of Sciences, 110(17), 6901-6906.

Katija, K., & Dabiri, J. O. (2009). A viscosity-enhanced mechanism for biogenic ocean mixing. Nature, 460(7255), 624.

Mass, T., Genin, A., Shavit, U., Grinstein, M., & Tchernov, D. (2010). Flow enhances photosynthesis in marine benthic autotrophs by increasing the efflux of oxygen from the organism to the water. Proceedings of the National Academy of Sciences, 107(6), 2527-2531.

Morgan, S. G., Shanks, A. L., Fujimura, A. G., Reniers, A. J., MacMahan, J., Griesemer, C. D., Jarvis, M. & Brown, J. (2016). Surfzone hydrodynamics as a key determinant of spatial variation in rocky intertidal communities. Proceedings of the Royal Society B: Biological Sciences, 283(1840), 20161017.

Shishido, C. M., Woods, H. A., Lane, S. J., Toh, M. W. A., Tobalske, B. W., & Moran, A. L. (2019). Polar gigantism and the oxygen–temperature hypothesis: a test of upper thermal limits to body size in Antarctic pycnogonids. Proceedings of the Royal Society B, 286(1900), 20190124.

Stocking, J. B., Laforsch, C., Sigl, R., & Reidenbach, M. A. (2018). The role of turbulent hydrodynamics and surface morphology on heat and mass transfer in corals. Journal of the Royal Society Interface, 15(149), 20180448.

Timerman, D., & Barrett, S. C. (2018). Divergent selection on the biomechanical properties of stamens under wind and insect pollination. Proceedings of the Royal Society B, 285(1893), 20182251.

6. Immunotherapy and the mechanisms of CAR T cell therapy (Debby Walser-Kuntz)

CAR (chimeric antigen receptor) T cells were first approved by the FDA for their role in treating cancers of the blood. However, CAR T cells may be an effective form of immunotherapy for tissue transplant rejection, autoimmunity, or HIV infection. CAR T cells can be activated to kill target cells, or in the case of CAR T regulatory cells, to dampen a response.

Explore an aspect of current CAR T cell therapy, focusing on the signaling pathways, regulation of key surface molecule expression, and the challenges of  determining CAR T cell efficacy in vivo. Your synopsis should explain the underlying immune mechanisms involved in the design and function of CAR T cells and address the role and impact of the specific phenotype of CAR T cells, structural variations in CARs, and T cell exhaustion.

Recommended courses: Immunology (Bio 310) or Virology (Bio 370)

Kansal, R. et al., 2019. Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Science Translational Medicine 11.  

Leick, M. & M. Maus. 2019. CAR T cells beyond CD19, UnCAR-Ted territory. American Journal of Hematology 94: S34-S41.

Wagner, T. 2018. Quarter century of anti-HIV CAR T cells. Current HIV/AIDS Reports 15:147–154.

Zhang, Q. et al. 2018. Chimeric Antigen Receptor (CAR) Treg: A promising approach to inducing immunological tolerance. Frontiers in Immunology 9: 1-8. 

7. Breaking Symmetry (Jennifer Wolff)

The establishment of each of the primary embryonic axes (anterior-poster, dorsal-ventral, and left-right) is key to the structure and function of living organisms. Formation of the embryonic anterior-posterior and dorsal-ventral axes is critical to survival in early embryos, and has been well studied by developmental biologists for over a century. In contrast, asymmetries on the left-right axis, such as the looping of digestive system and heart and “handedness” of nervous system structures, are somewhat subtle, with their molecular and cellular origins, until recently, less well understood.

Identify a tissue or organ that exhibits asymmetry on the left-right axis, and discuss how this asymmetry contributes to its function. Describe the molecular and cellular processes by which this asymmetry develops, tracing a path from initial symmetry breaking through later events such as asymmetric morphogenesis, cell division, and gene expression.

Recommended courses: BIOL240, BIOL280, BIOL342, or BIOL368

Desgrange, A., Le Garrec, J.-F., and Meilhac, S.M. (2018). Left-right asymmetry in heart development and disease: forming the right loop. Development 145, dev162776–19.

Duboc, V., Dufourcq, P., Blader, P., and Roussigné, M. (2015). Asymmetry of the Brain: Development and Implications. Annu. Rev. Genet. 49, 647–672.

Grimes, D.T., and Burdine, R.D. (2017). Left–Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis. Trends in Genetics 33, 616–628.

Levin, M., Klar, A.J.S., and Ramsdell, A.F. (2016). Introduction to provocative questions in left–right asymmetry. Phil. Trans. R. Soc. B 371, 20150399–7.

Zhang, H.T., and Hiiragi, T. (2018). Symmetry Breaking in the Mammalian Embryo. Annu Rev Cell Dev Biol 34, 405–426. 

8. Reproductive Physiology (Matt Rand)

Physiology is an essential mediator of the reproductive phenotype. The regulatory mechanisms of reproduction through the hypothalamo-pituitary-gonad axis are fairly well understood for vertebrates, including humans. However, a comprehensive understanding of reproductive biology should include the mechanisms responsible for the onset and cessation of reproductive events, whether typical or anomalous. Information on how reproduction is initiated, ended, or interrupted by normal physiological means, environmental perturbations, or pathologies, is less well understood.

Choose a reproductive function or anomaly (e.g. sexual maturation, induced ovulation, early menarche, end-of-season gonadal quiescence, menopause, infertility, amenorrhea, reduced sperm count, etc.) and review the current literature in an attempt to understand the physiological mechanisms that mediate your chosen sample of the reproductive phenotype.

Recommended courses: Environmental Animal Physiology (252), Human Physiology (332), Human Reproduction and Sexuality (101), and/or Animal Development (342)

Angelopoulou, E., C. Quignon, L.J. Kriegsfeld, V. Simonneaux (2019) Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction. Front Endocrinol (Lausanne) 10;183: 1-14.

Hart, R.J. (2016) Physiological aspects of female fertility: Role of the environment, modern lifestyle, and genetics. Physiol Rev 96: 873–909.

Leonardi, A., M. Cofini, D. Rigante, L. Lucchetti, C. Cipolla, L. Penta, and S. Esposito (2017) The Effect of Bisphenol A on Puberty: A Critical Review of the Medical Literature. Int J Environ Res Public Health 14;1044:1-20.

Maranesi, M., L. Petrucci, L. Leonardi, F. Piro, P.G. Rebollar, P. Millán, P. Cocci, C. Vullo, F. Parillo, A.M.G.G. Mariscal, C. Boiti, M. Zerani (2018) New insights on a NGF-mediated pathway to induce ovulation in rabbits (Oryctolagus cuniculus). Biol Reprod 1;98: 634-643.

See previous years’ comps questions