2021–2022 Comps Questions
1. Structure and Function of Cilia (Wolff)
You may be familiar with cilia (sometimes known as flagella) as the beating structures that propel sperm and help clear the lungs of mucus. However, cilia do so much more–they are involved in many aspects of development and homeostasis, including olfactory reception, kidney regulation, and developmental patterning of both the overall body plan and individual tissues (such as the brain and limb). Defects in cilia structure and function lead to a range of phenotypes and disorders in humans, including polycystic kidney disease, situs inversus, hydrocephaly, blindness, obesity, infertility, and some cancers. Choose an example in which cilia structure or function contributes to development or homeostasis. For this example, 1) discuss how structural components of the cilia enable their motility or signaling capacity to support the normal development or homeostasis of a tissue or organ; and 2) explain how defects in cilia structure or function lead to a disease or disorder.
Recommended courses: Cell biology, Genetics, Topics in Developmental Biology, Human Physiology, Developmental Neurobiology
- Reiter, J. F. and Leroux, M. R. (2017). Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 18, 533-547. doi:10.1038/ nrm.2017.60 https://www.nature.com/articles/nrm.2017.60
- Liu, H., Kiseleva, A.A., and Golemis, E.A. (2018) Ciliary signaling in cancer. Nat Rev Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448793/
- Spassky, N. and Meunier, A. (2017) The development and function of multiciliated epithelia. Nat Rev Mol Cell Biol https://www.nature.com/articles/nrm.2017.21
- Hasenpusch-Theil K. and Theil T. (2021) The Multifaceted Roles of Primary Cilia in the Development of the Cerebral Cortex. Front, Cell Dev. Biol. https://doi.org/10.3389/fcell.2021.630161
2. Genomic plasticity in microbes (Anderson, winter-spring only)
One of the more notable discoveries of the biological sequencing revolution has been the remarkable flexibility of microbial genomes. This occurs through the processes of gene loss, gene duplication, and especially horizontal gene transfer. As a result, even closely related strains of archaea and bacteria can have wide variation in genome content. The gain or loss of genes can enable individual lineages within a given species to gain new functions and adapt to specialized conditions. The collection of genes that characterize a given species or genus is called the “pangenome,” with the “core genome” containing genes present in all strains, and the “variable genome” reflecting genes found in only certain strains. For a specific microbial species/genus or microbiome, investigate how genomic plasticity manifests and how it affects the ecology or evolution of those microbes.
Recommended courses: Genomics & Bioinformatics or Microbiology
- Brockhurst MA, Harrison E, Hall JPJ, Richards T, McNally A, MacLean C (2019) The Ecology and Evolution of Pangenomes. Current Biology.
- Delmont TO, Eren AM (2018) Linking pangenomes and metagenomes: the Prochlorococcus metapangenome. PeerJ 6, e4320.
- Hall JPJ, Brockhurst MA, Harrison E (2017) Sampling the mobile gene pool: Innovation via horizontal gene transfer in bacteria. Philosophical Transactions of the Royal Society B: Biological Sciences.
- McInerney JO, McNally A, O’Connell MJ (2017) Why prokaryotes have pangenomes. Nature Microbiology 2, 17040.
- McInnes RS, McCallum GE, Lamberte LE, Schaik W van (2020) Horizontal transfer of antibiotic resistance genes in the human gut microbiome. Current Opinion in Microbiology.
3. Alternative splicing and disease (Zweifel)
Alternative splicing of protein-coding messenger RNAs is an essential regulatory mechanism in eukaryotic gene expression. Genomic studies indicate that alternative splicing plays a major role in the generation of proteomic diversity, and disruption of the alternative splicing mechanism has a determinative role in disease. In fact, a growing body of work highlights the importance of alternatively spliced isoforms in neurodegenerative disorders, cancer, immune and infectious diseases, cardiovascular diseases, metabolic conditions, and aging. The development of techniques such as next generation sequencing and CRISPR has greatly enhanced the understanding of mis-splicing. Examine the current understanding of alternative splicing mechanisms, the role of transcription variants in normal and disease physiology, and potential therapeutic strategies.
One or more of the following are recommended: Genetics, Cell Biology, sense of adventure.
- Bhadra, M., Howell, P., Dutta, S., Heintz, C., and Mair, W.B. (2020). Alternative splicing in aging and longevity. Hum. Genet. 139, 357–369.
- Black, A.J., Gamarra, J.R., and Giudice, J. (2019). More than a messenger: Alternative splicing as a therapeutic target. Biochim. Biophys. Acta. Gene Regul. Mech. 1862, 194395.
- Montes, M., Sanford, B.L., Comiskey, D.F., and Chandler, D.S. (2019). RNA Splicing and Disease: Animal Models to Therapies. Trends Genet. 35, 68–87.
- Ule, J., and Blencowe, B.J. (2019). Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution. Mol. Cell 76, 329–345.
4. Immune memory (Walser-Kuntz)
A hallmark of the adaptive immune response in vertebrates is the generation of memory B and T lymphocytes that protect against future infection. The production of neutralizing antibodies has been key to the success of many of our vaccines, however our understanding of the development and persistence of memory B cells and long-lived plasma cells is still unfolding. Explore the factors that contribute to our current understanding of the generation of memory B cells or long-lived plasma cells including changes in metabolism, transcriptional regulation, activation of signaling pathways, interaction with T follicular helper cells, and/or the formation of the germinal center where competitive selection of the highest affinity antibody allows for evolution of the adaptive immune response.
One or more of the following courses are recommended: Immunology or Behavioral neuroimmunology; supporting courses include Biochemistry, Cell Biology, Genetics, or Animal Development
- Akkaya, M., K. Kwak, and Pierce, S.K. (2020). B cell memory: building two walls of protection against pathogens. Nat. Rev. Immunol. 20, 229–238. https://www.nature.com/articles/s41577-019-0244-2
- Quast, I. and D. Tarlinton. (2021). B cell memory: understanding COVID-19. Immunity. 54, 2015-210. https://doi.org/10.1016/j.immuni.2021.01.014
- Ripperger, T. and D. Bhattacharya. (2021). Transcriptional and Metabolic Control of Memory B Cells and Plasma Cells. Ann. Rev. Imm. 39, 345-368. https://doi.org/10.1146/annurev-immunol-093019-125603
- Suan, D., C. Sundling, and R. Brink. (2017). Plasma cell and memory B cell differentiation from the germinal center. Current Opinion in Immunology. 45, 97-102. https://www.sciencedirect.com/science/article/abs/pii/S0952791517300316
5. How do species interactions determine outcomes for ecosystem restoration? (Hernández or McKone)
Ecosystem restorations are commonly performed by returning plant species to a location where they have been lost, with the hope that ecological relationships and ecosystem functions will then be passively reestablished over time. However, recent studies have suggested that species interactions (e.g., mutualism, predation, and disease) between plants and other organisms may determine the ultimate success of the restoration and should be explicitly considered in our restoration approaches. For this question, you should consider the ways in which species interactions are important (or unimportant!) to the success of ecosystem restorations and how restoration approaches could be modified to incorporate species interactions.
Recommended courses: Ecosystem ecology and/or Population Ecology
- Derksen‐Hooijberg, M., C. Angelini, L. P. M. Lamers, A. Borst, A. Smolders, J. R. H. Hoogveld, H. de Paoli, J. van de Koppel, B. R. Silliman, T. van der Heide. 2017. Mutualistic interactions amplify saltmarsh restoration success. Journal of Applied Ecology 55: 405-414.
- Guiden, P. W., N. A. Barber, R. Blackburn, A. Farrell, J. Fliginger, S. C. Hosler, R. B. King, M. Nelson, E. G. Rowland, K. Savage, J. P. Vanek, H. P. Jones. 2021. Effects of management outweigh effects of plant diversity on restored animal communities in tallgrass prairies. PNAS 118.
- Koziol, L., P. A. Schultz, G. L. House, J. T. Bauer, E. L. Middleton, J. D. Bever. 2018. The plant microbiome and native plant restoration: the example of native mycorrhizal fungi. BioScience 68: 996-1006.
- Ladd, M. C., M. W. Miller, J. H. Hunt, W. C. Sharp, D. E. Burkepile. 2018. Harnessing ecological processes to facilitate coral restoration. Frontiers in Ecology and the Environment 16: 239-247
6. Impact of fire (McKone or Hernández)
Fire has had a major impact on terrestrial biota throughout Earth’s history. With anthropogenic modification of global systems, fire frequency has been decreased in some areas due to fire suppression; but elsewhere severe wildfires have become much more common. Explore the impact of fires on some aspect of populations, communities, or ecosystems. Potential topics include how species have evolved to adapt to frequent fires; how fire shapes community composition of forests, grasslands, or other ecosystems; how recent human-caused change in fire frequency has modified ecosystem properties; and how climate change is modifying fire frequency.
Recommended courses: Evolution, Population Ecology, Ecosystems Ecology, or Landscape Ecology
- Causley, C. L., W. M. Fowler, B. B. Lamont, and T. He. 2016. Fitness benefits of serotiny in fire- and drought-prone environments. Plant Ecology 217:773–779. DOI: 10.1007/s11258-015-0552-y
- Collins, S. L., J. B. Nippert, J. M. Blair, J. M. Briggs, P. Blackmore, and Z. Ratajczak. 2021. Fire frequency, state change and hysteresis in tallgrass prairie. Ecology Letters 24:636–647. DOI:10.1111/ele.13676
- Kelly, L. T., K. M. Giljohann, A. Duane, N. Aquilué, S. Archibald, E. Batllori, A. F. Bennett, et al. 2020. Fire and biodiversity in the Anthropocene. Science 370:eabb0355. DOI:10.1126/science.abb0355
- Turner, M. G., K. H. Braziunas, W. D. Hansen, and B. J. Harvey. 2019. Short-interval severe fire erodes the resilience of subalpine lodgepole pine forests. Proceedings of the National Academy of Sciences of the United States of America 166:11319–11328. DOI: 10.1073/pnas.1902841116
7. Molecular-genetic and optogenetic approaches to the treatment of neurodegenerative disorders (Jaramillo)
As our population ages, neurodegenerative diseases are expected to take a growing toll on the nation’s well-being and medical costs. Although progress on the treatment of neurodegenerative disorders has been painfully slow, new advances in molecular-genetic and optogenetic techniques could dramatically increase the speed of therapeutic discovery. Review recent developments in these techniques and the nascent impact they are having on our ability to treat these vexing diseases.
One or more of the following courses are recommended: Neurobiology, Topics in Neuroscience, Human Physiology, Neurons, Circuits, and Behavior
- Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713–1722 (2017).
- Hudry, E. & Vandenberghe, L. H. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron 102, 839–862 (2019).
- Finkel, R. S. et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med. 377, 1723–1732 (2017).
- Ordaz JD, Wu W, Xu XM. Optogenetics and its application in neural degeneration and regeneration. Neural Regen Res. 2017
- Valverde, S., Vandecasteele, M., Piette, C. et al. Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms. Nat Commun11, 2388 (2020). https://doi.org/10.1038/s41467-020-16046-6