1. Cancer immunotherapies (Debby Walser-Kuntz, Winter/Spring only) 

As our understanding of immune system functioning continues to increase, we have been able to design several immunotherapies for cancer. The design of these therapies requires a deep understanding of the mechanisms of how the immune system recognizes and responds to “danger”, i.e. the presence of either a foreign invader or a transformed cancer cell. Explore the biological mechanisms behind a recent immunotherapy approach for cancer that is either under development or currently being used to treat patients. Your paper should include signaling pathways, metabolic changes that occur in the immune cells, and/or explanations of the function of the molecules being manipulated in the therapeutic approach. You may focus on either antibody-mediated or cellular therapies that involve  natural killer (NK) or T cells.  

Recommended courses:

Immunology (strongly recommended), Survey of Biochemistry, Cell Biology

Suggested reading:

Bodmer, W. and V. Golubovskaya. (2023) Cancer Immunotherapy: Where Next? Cancers. 15: 2358-2369.

Kyrysyuk, O. and K. Wucherpfennig. (2023) Designing Cancer Immunotherapies That Engage T Cells and NK Cells. Annual Review of Immunology. 41:17-38.

Leone, R. and J. Powell (2021) Fueling the Revolution: Targeting Metabolism to Enhance Immunotherapy. Cancer Immunol Res. 9: 255–260.

Waldman, A., Fritz, J., and M. Lenardo. (2020). A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nature Rev Imm. 20:651–668.  

  1. Life at the ocean’s edge  (Mike Nishizaki) 

The intertidal zone, where the ocean meets the land, alternates between exposure to air at low tide and submersion at high tide. This unique environment hosts a diverse array of invertebrates, vertebrates, angiosperms, and seaweeds, all adapted to withstand fluctuations in temperature, moisture, salinity, and wave action. How future climate change may or may not change these environmental conditions and the responses of organisms to these changes remains unclear.  

This question will address the potential effects of climate change on intertidal organisms with an explicit focus on the experience of life in both air and water.

Recommended courses: 

Ecological Physiology, Ecological Biomechanics 

Suggested reading:

Gilman, S., Ober, G. T., Rognstad, R. L., Bunnenberg-Ross, M., & Man, T. (2024). Geographic variation in vulnerability to warming temperatures in an intertidal barnacle species. bioRxiv, 2024-03.

Helmuth, B., Mieszkowska, N., Moore, P., & Hawkins, S. J. (2006). Living on the edge of two changing worlds: forecasting the responses of rocky intertidal ecosystems to climate change. Annu. Rev. Ecol. Evol. Syst., 37, 373-404.

Seabra, R., Wethey, D. S., Santos, A. M., Gomes, F., & Lima, F. P. (2016). Equatorial range limits of an intertidal ectotherm are more linked to water than air temperature. Global Change Biology, 22(10), 3320-3331.

Thyrring, J., Blicher, M. E., Sørensen, J. G., Wegeberg, S., & Sejr, M. K. (2017). Rising air temperatures will increase intertidal mussel abundance in the Arctic. Marine Ecology Progress Series, 584, 91-104.

Yin, X., Chen, P., Chen, H., Jin, W., & Yan, X. (2017). Physiological performance of the intertidal Manila clam (Ruditapes philippinarum) to long-term daily rhythms of air exposure. Scientific Reports, 7(1), 41648.

Zuelow, A. N., Roberts, K. T., Burnaford, J. L., & Burnett, N. P. (2024). Freezing and mechanical failure of a habitat-forming kelp in the rocky intertidal zone. Integrative and Comparative Biology, icae007.

  1. Global change and ecological drivers of spillover (John Berini)

Spillover occurs when a species-specific parasite or pathogen infects a novel host. For spillover to occur, the parasite or pathogen must overcome several obstacles, not the least of which is that a successful event requires spatial and temporal alignment between an infected host and a novel, susceptible species. While these events are considered to be extremely rare, recent evidence suggests that the rate of spillover is steadily increasing, with factors associated with global change (e.g., climate and landscape change) indicated as major drivers of this increase. Moreover, changes to the use and availability of critical resources can alter the likelihood of the spatial and temporal alignment needed for a spillover event to occur.

For this question, you will investigate how a specific aspect of global change (e.g., climate change, landscape change, biodiversity, invasive species, etc.) influences the likelihood of spillover via its effect on various ecological drivers. Alternatively, you can focus your response on how a single ecological driver is influenced by various aspects of global change. 

Recommended Course: 

Disease Ecology, Global Change Biology, Population Ecology

Suggested Reading:

Becker, D. J., Eby, P., Madden, W., Peel, A. J., and R. K. Plowright (2023) Ecological conditions predict the intensity of Hendra virus excretion over space and time from bat reservoir hosts. Ecology Letters 26: 23-36

Borremans, B., Faust, C.,  Manlove, K. R., Sokolow, S. H., and J. O. Lloyd-Smith (2019) Cross-species pathogen spillover across ecosystem boundaries: mechanisms and theory. Philosophical Transactions of the Royal Society B 374: 20180344

Eby, P.,  Peel, A. J., Hoegh, A., Madden, W., Giles, J. R., Hudson, P. J., and R. K. Plowright (2022) Pathogen spillover driven by rapid changes in bat ecology. Nature 613: 340 – 345.

Faust, C. L., McCallum, H. I., Bloomfield, L. S. P., Gottdenker, N. L., Gillespie, T. R., Torney, C. J., Dobson, A. P., and R. K. Plowright (2018) Pathogen spillover during land conversion. Ecology Letters 21: 471-483.

Oliveira-Santos, L. G. R., Moore, S. A., Severud, W. J., Forester, J. D., Isaac, E. J., Chenaux-Ibrahim, Y., Garwood, T., Escobar, L. E., and T. M.  Wolf (2021) Spatial compartmentalization: A nonlethal predator mechanism to reduce parasite transmission between prey species. Science Advances 7: eabj5944.

Plowright, R. K., Ahmed, A. N., Coulson, T., Crowther, T. W., Ejotre, I., Faust, C. L., Frick, W. F., Hudson, P. J., Kingston, T., Nameer, P. O. and M. T. O’Mara (2024) Ecological countermeasures to prevent pathogen spillover and subsequent pandemics. Nature Communications 15: 2577.

Rayl, N. D., Merkle, J. A., Proffitt, K. M., Almberg, E. S., Jones, J. D., Gude, J. A., & P. C. Cross (2021) Elk migration influences the risk of disease spillover in the Greater Yellowstone Ecosystem. Journal of Animal Ecology 90:1264–1275.

  1. Gene flow across eukaryotic species boundaries (Mark McKone)

According to the classical Biological Species Concept, eukaryotic species are defined by lack of gene flow between lineages.  But recent evidence has shown that rare gene flow events between separately evolving lineages can have profound impacts on subsequent evolution.  Such events can occur by two mechanisms: (1) introgression via hybridization between closely related lineages and (2) horizontal gene transfer between distantly related lineages.  Review how these mechanisms have changed evolutionary history in one or more eukaryotic groups. 

Recommended Courses:

Evolution, Genomics and Bioinformatics, Genetics

Suggested Reading

Li, Y., Z. Liu, C. Liu, Z. Shi, L. Pang, C. Chen, Y. Chen et al. 2022.  Horizontal gene transfer is widespread in insects and contributes to male courtship in lepidopterans. Cell 185:2975-2987.

doi.org/10.1016/j.cell.2022.06.014

Rosser, N., F. Seixas, L.M. Queste, B. Cama, R.Mori-Pezo, D. Kryvokhyzha, M. Nelson et al. 2024. Hybrid speciation driven by multilocus introgression of ecological traits. Nature 628:811–817

doi.org/10.1038/s41586-024-07263-w

Sørensen, E.F., R.A. Harris, L. Zhang, M. Raveendran, L.F.K. Kuderna, J.A. Walker, J.M. Storer et al. 2023. Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons. Science 380:eabn8153.

doi.org/10.1126/science.abn8153

Walker, A.A., S.D. Robinson, D.J. Merritt, F.C. Cardoso, M.H. Goudarzi, R.S. Mercedes, D.A. Eagles et al. 2023. Horizontal gene transfer underlies the painful stings of asp caterpillars (Lepidoptera: Megalopygidae). Proceedings of the National Academy of Sciences 120:e2305871120.

doi.org/10.1073/pnas.2305871120

  1. Sex Differences in Physiology and Health (Matt Rand, Fall/Winter only)

Understanding the sex differences in physiology and disease susceptibility is essential for creating and promoting sex-specific healthcare, as well as supporting health equity for all individuals. Sex-typical genotypic and phenotypic differences among individuals can influence various aspects of physiology which may influence metabolism, skeletomuscular function, reproduction, cardiovascular health, autoimmune variation, and mental and neurological health, to name a few. In addition, there is growing evidence that environmental toxins such as endocrine disruptors (pesticides, herbicides, and plasticizers) and nanoplastics have differential effects on an individual depending on their sex. Choose a topic related to sex differences that interests you and summarize the evidence that supports the differential effects of sex on health and/or physiological function. It will be essential to understand and explain the physiological, cellular, and/or molecular mechanisms involved with the topic you choose.

Recommended Courses

Animal Physiology, Human Physiology, Cell Biology, or Survey of Biochemistry.

Suggested Reading

Dion-Albert, L., L. Bandeira-Binder, B. Daigle, A. Hong-Minh, M. Lebel, and C. Menard (2022) Sex differences in the blood-brain barrier: Implications for mental health. Front. Neuroendocrinol. 65:100989. DOI: 10.1016/j.yfrne.2022.100989

Drury, E. R., J. Wu, J. C. Gigliotti, and T. H. Le (2023) Sex differences in blood pressure regulation and hypertension: renal, hemodynamic, and hormonal mechanisms. Physiol. Rev.16:199-251. https://doi.org/10.1152/physrev.00041.2022

Le Magueresse-Battistoni, B. (2020) Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter? Int. J. Environ. Res. Public Health 2020, 17, 9403. https://doi.org/10.3390/ijerph17249403

Palanza, P., S. Paterlini, M. Maddalena Brambilla, G. Ramundo, G. Caviola, L. Gioiosa, S. Parmigiani, F. S. vom Saal, and D. Ponzi (2021) Sex-biased impact of endocrine disrupting chemicals on behavioral development and vulnerability to disease: Of mice and children. Neurosci. Biobehav. Rev.,121:29-46. https://doi.org/10.1016/j.neubiorev.2020.11.015

Reue, K. and C. B. Wiese (2022) Illuminating the Mechanisms Underlying Sex Differences in Cardiovascular Disease. Circulation Research, 130:1747–1762. https://doi.org/10.1161/CIRCRESAHA.122.320259

  1. Unusual “organelles” (Raka Mitra)

If you were asked to name a few organelles, it is likely that you’d pick ones that are well known. Your list might include the nucleus, endoplasmic reticulum, Golgi apparatus, lysosome, mitochondria and chloroplast. But there are a number of other compartments or organelle-like regions of cells that perform important functions that are essential for cellular functioning.  For example, the lipid droplet, the peroxisome, the cilia, the pyrenoid, the magnetosome, or the nitroplast. There are many more unique cellular structures to explore.

For this comps question, you will investigate the workings of an unusual “organelle”, focusing on the cell biology, molecular biology and/or biochemistry of an essential process that occurs there. 

Recommended Courses: 

Cell Biology, Genetics, Survey of Biochemistry

Suggested Reading

Derderian, C., Canales, G.I., and Reiter, J.F. (2023). Seriously cilia: A tiny organelle illuminates evolution, disease, and intercellular communication. Developmental Cell 58, 1333–1349. 

https://doi.org/10.1016/j.devcel.2023.06.013.

Di Cara, F., Savary, S., Kovacs, W.J., Kim, P., and Rachubinski, R.A. (2023). The peroxisome: an up-and-coming organelle in immunometabolism. Trends in Cell Biology 33, 70–86. https://doi.org/10.1016/j.tcb.2022.06.001.

He, S., Crans, V.L., and Jonikas, M.C. (2023). The pyrenoid: the eukaryotic CO2-concentrating organelle. The Plant Cell 35, 3236–3259. 

https://doi.org/10.1093/plcell/koad157.

Jin, Y., Tan, Y., Wu, J., and Ren, Z. (2023). Lipid droplets: a cellular organelle vital in cancer cells. Cell Death Discov. 9, 1–9. 

https://doi.org/10.1038/s41420-023-01493-z.

Massana, R. (2024). The nitroplast: A nitrogen-fixing organelle. Science 384, 160–161. https://doi.org/10.1126/science.ado8571.

Taoka, A., Eguchi, Y., Shimoshige, R., and Fukumori, Y. (2023). Recent advances in studies on magnetosome-associated proteins composing the bacterial geomagnetic sensor organelle. Microbiology and Immunology 67, 228–238. https://doi.org/10.1111/1348-0421.13062.

  1. Cooperation makes it happen (Rika Anderson, Fall/Winter only)

Across diverse ecosystems, microbes live in dense communities, and they have evolved to cooperate in surprising ways. Some microbes form tight partnerships in which they depend on each other for the exchange of nutrients or energy sources through what is called syntrophy. Other microbes communicate and coordinate with each other to form biofilms or turn on luminescent proteins through a process called quorum sensing. Still others live in a state of endosymbiosis, in which one microbe lives inside the other. Investigate a question related to one specific type of microbial cooperation: For example, how do the microbes cooperate, and what mechanisms do they use? What is the nature of the cooperative relationship? How did that cooperative relationship evolve? Are metabolites or energy sources shared, and if so, what are the consequences for the ecosystem or for biogeochemical cycling?

Recommended courses:

Microbiology, Genomics and Bioinformatics, Ecosystem Ecology, or Evolution

Suggested reading:

  • Coale, T., Loconte, V., Turk-Kubo, K., Vanslembrouck, B., Mak, W., Cheung, S., Ekman, A., Chen, J-H., Hagino, K., Takano, Y., Nishimura, T., Adachi, M., Le Gros, M., Larabell, C., and Zehr, J. (2024) Nitrogen-fixing organelle in a marine alga. Science 384, 217-222.

Huang, Y., Roux, S., Coclet, C., Krause, S., and Girguis, P. (2023) Viruses interact with hosts that span distantly related microbial domains in dense hydrothermal mats. Nature Microbiology (2023) 8, 946-957.

  • Mashruwala, A. and Bassler, B. (2020) The Vibrio cholerae quorum-sensing protein VqmA integrates cell density, environmental, and host-derived cues into the control of virulence. mBio 11:10.1128/mbio.01572-20.
  • Oliviera, M., Niehus, R., and Foster, K. (2014) Evolutionary limits to cooperation in microbial communities. Proceedings of the National Academy of Sciences, U.S.A. 111 (50), 17941-17946
  • Morris, B., Henneberger, R., Huber, H., Moissl-Eichinger, C. (2013) Microbial syntrophy: interaction for the common good. FEMS Microbiology Reviews 37(3), 384-406
  • Wurch, L., Giannone, R., Belisle, B., Swift, C., Utturkar, S., Hettich, R., Reysenbach, A-L., and Podar, M. (2016) Genomics-informed isolation and characterization of a symbiotic Nanoarchaeota system from a terrestrial geothermal environment. Nature Communications 7, 12115