Biology Comps Questions 2022-23

1. Pre-mRNA splicing (Mitra) 

Gene expression can be regulated in a number of ways. In eukaryotes, transcription results in the production of a messenger RNA precursors (pre-mRNAs) and protein-coding segments, the exons, must be spliced together to form mature messenger RNAs (mRNAs). This essential process is known as pre-mRNA splicing. The mechanism of splicing is well studied in human and yeast systems, and involves over one hundred proteins and five small nuclear RNAs (snRNAs). These components assemble as part of the spliceosome, which is formed on its substrate during splicing. Of the approximately 20,000 human protein coding genes, 95% are alternatively spliced. A single gene can produce multiple protein isoforms expanding the proteome that can be derived from a limited number of genes. Thus, pre-mRNA splicing contributes to the vast complexity of higher organisms. 

Examine the role of a small group of spliceosomal components, describing their molecular functions, and investigate how proper functioning of these components is essential for one or more biological processes. Focus on the cellular, molecular and biochemical level, and highlight open questions in this area. 

Note: This question relates to a discovery made by students in Cell Biology lab in Fall 2021. We found that a bacterial wilt pathogen effector protein may bind and target a tomato splicing factor. One of the next steps in this project is to learn more about the process of pre-mRNA splicing. 

Recommended courses: Cell Biology and/or Biochemistry

Suggested reading:

  • Gehring, N.H., and Roignant, J.-Y. (2021). Anything but Ordinary – Emerging Splicing Mechanisms in Eukaryotic Gene Regulation. Trends in Genetics 37, 355–372. 
  • Plaschka, C., Newman, A.J., and Nagai, K. (2019). Structural Basis of Nuclear pre-mRNA Splicing: Lessons from Yeast. Cold Spring Harb Perspect Biol 11, a032391. 
  • Ule, J., and Blencowe, B.J. (2019). Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution. Molecular Cell 76, 329–345. 
  • Wilkinson, M.E., Charenton, C., and Nagai, K. (2020). RNA Splicing by the Spliceosome. Annual Review of Biochemistry 89, 359–388. 

2. Microbial response to climate change (Anderson)

Since life first began on Earth, microbes have both affected and responded to climatic change through innovation of new metabolisms, adapting to dynamic habitats, and radiating into new ecological niches. Now, in the Anthropocene, climate is changing at a faster rate than we have seen for millions of years due to the burning of fossil fuels. This global change has vast implications for marine and terrestrial microbial ecology, agriculture, and infectious disease. As climate changes, microbial ecosystems must adapt and diversify; conversely, global biogeochemical cycles and the climate are strongly influenced by microbial metabolism and adaptation. Choose a specific microbiome or habitat and examine how the microbes in that ecosystem have responded to climatic change, and how the microbial response feeds back to the climate system and global biogeochemical cycles.

Recommended courses: Genomics and Bioinformatics or Microbiology or Ecosystem Ecology

Suggested Reading:

3. Immune evasion and viruses (Walser-Kuntz) 

The vertebrate immune system has evolved multiple mechanisms for anti-viral defense, including host restriction factors and innate, antibody, natural killer, and cytotoxic T cell responses. However, many pathogenic viruses, including herpes, coronaviruses, Zika, hepatitis, and HIV have co-evolved to evade these protective responses. Viruses may cause disease by avoiding pattern recognition receptors, downregulating key surface proteins, crossing tight junctions to avoid antibody detection, interrupting signaling pathways, or targeting host proteins for destruction. Depending on your course background, you may choose to explore an aspect of this co-evolutionary arms race by focusing more heavily on either the viral proteins involved in immunoevasion or the molecular mechanisms and components of the immune system that are targeted by a viral pathogen. 

Recommended courses: Virology and/or Immunology

Suggested Reading:

  • Estevez-Herrera, J. et al, (2021). Zika Virus Pathogenesis: A Battle for Immune Evasion. Vaccines 9, 294.  
  • Jasinski-Bergner, S., Mandelboim, O., and Seliger, B. (2020). Molecular mechanisms of human herpes viruses inferring with host immune surveillance. J Immunother Cancer 8, 1-11.
  • Kikkert, M. (2020) Innate Immune Evasion by Human Respiratory RNA Viruses. J Innate Immununity12, 4-20.
  • Ortega-Prieto, A., and Dorner, M. (2017). Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection. Vaccines 5, 1-26.
  • Zhua, H., and Zheng, C. (2020). The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1. Microbiology and Molecular Biology Reviews 84.

4. Life in fluctuating environments (Nishizaki)

In this age of climate change, the biological impacts of environmental stress have been documented in terrestrial, freshwater, and marine ecosystems around the world. Historically, biologists have employed measures of central tendency to help describe the impacts of various environmental processes (e.g., temperature, pH, light, salinity, precipitation) on physiological, behavioral, and ecological traits. Most natural environments, however, are characterized by fluctuating conditions (e.g., on April 29, 2022, a heatwave in India spiked temperatures to 62°C/143°F). The aim of this question is to explore the potential roles that both variation and central tendency have in shaping our understanding of the interaction between environmental conditions and biological responses. Appropriately focused questions may synthesize evidence from any taxonomic group and type of ecosystem.

“Variation is the hard reality, not a set of imperfect measures for a central tendency. Means and medians are the abstractions.”  – Stephen Jay Gould 

Recommended courses: Ecological physiology, Ecomechanics, Climate change beneath the waves, and/or Integrative animal physiology. Biostatistics may also be helpful, but not required.

Suggested reading:

  • Basan, M., Honda, T., Christodoulou, D., Hörl, M., Chang, Y. F., Leoncini, E., … & Sauer, U. (2020). A universal trade-off between growth and lag in fluctuating environments. Nature, 584(7821), 470-474.
  • Denny, M. W., & Dowd, W. W. (2021). Physiological consequences of oceanic environmental variation: life from a pelagic organism’s perspective. Annual Review of Marine Science, 14.
  • Dillon, M. E., Woods, H. A., Wang, G., Fey, S. B., Vasseur, D. A., Telemeco, R. S., … & Pincebourde, S. (2016). Life in the frequency domain: the biological impacts of changes in climate variability at multiple time scales. Integrative and comparative biology, 56(1), 14-30.
  • Leach, T. S., BuyanUrt, B., & Hofmann, G. E. (2021). Exploring impacts of marine heatwaves: paternal heat exposure diminishes fertilization success in the purple sea urchin (Strongylocentrotus purpuratus). Marine Biology, 168(7), 1-15.
  • Paniw, M., Maag, N., Cozzi, G., Clutton-Brock, T., & Ozgul, A. (2019). Life history responses of meerkats to seasonal changes in extreme environments. Science, 363(6427), 631-635. 

5. Heterogeneity in Alzheimer’s Disease (Jaramillo, Fall/Winter only)

Recently, and despite weak evidence of its effectiveness, the FDA approved aducanumab, an enormously expensive drug for the treatment of Alzheimer’s disease. But the truth is we don’t know what causes Alzheimer’s! Indeed, the heterogeneity of Alzheimer’s suggests there may be several disorders covered under the same name. Explore this heterogeneity, focusing on possible links of the disease to tau proteins and microglia.

Recommended Courses: Neurobiology (biol386), Topics in neuroscience (biol365), Cell Biology (biol280).

Suggested reading: 

  • S.C. Hopp, et al. The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease. J. Neuroinflammation, 15 (2018), p. 269
  • J. Zou, et al. Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment. Neurobiol. Aging, 85 (2020), pp. 11-21
  • S. Dujardin, et al. Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease. Nat. Med., 26 (2020), pp. 1256-1263

6. The ecological impacts of non-conventional agricultural practices. (Hernández)

The widespread use of conventional western agricultural practices (i.e., large-scale monoculture cropping systems using inorganic fertilizer inputs or single-species livestock systems with high-intensity, high-duration grazing regimes) has had widespread ecological impacts: declines in local and regional biodiversity, reduced soil carbon storage, increased nutrient pollution, and increased habitat fragmentation. There have been a wide range of alternative practices proposed to help mitigate the ecological impacts of agriculture, including no-till, cover crops, rotational or patch-burn grazing, polyculture, integrated plant-animal systems, and many others. For this question, consider the evidence for the ways in which one or more of these non-conventional practices influence community or ecosystem processes in agroecological systems.  

Recommended courses: Agroecology, Ecosystem Ecology, Global Change Biology, Grassland Ecology, and/or Population Ecology

Suggested reading: 

  • Beillouin, D., T. Ben-Ari, E. Malézieux, V. Seufert, D. Makowski. 2021. Positive but variable effects of crop diversification on biodiversity and ecosystem services. Global Change Biology 27: 4697-4710.
  • Brewer, K. and A.C.M. Gaudin. 2020. Potential of crop-livestock integration to enhance carbon sequestration and agroecosystem functioning in semi-arid croplands. Soil Biology and Biochemistry 149: 107936.
  • Tscharntke, T., I. Grass, T.C. Wanger, C. Westphal, and P. Batáry. 2021. Beyond organic farming: harnessing biodiversity-friendly landscapes. Trends in Ecology and Evolution 36: 919-930.
  • Sitters, J., D.M. Kimuyu, T.P. Young, P. Claeys, H.O. Venterink. 2020. Negative effects of cattle on soil carbon and nutrient pools reversed by megaherbivores. Nature Sustainability 3: 360-366.
  • Zomer, R.J., D.A Bossio, R. Sommer, and L.V. Verchot. 2017. Global sequestration potential of increased organic carbon in cropland soils. Scientific Reports 7: 15554.

7. Codon-usage bias and its role in gene expression (Zweifel)

Because of the degeneracy of the genetic code, synonymous codon changes (base pair mutations which do not alter amino acid sequence) were initially thought to have no functional consequence with regards to protein expression.  In fact, many genetic textbooks still refer to synonymous mutations as “silent mutations”.  However, in most genomes that have been sequenced, synonymous codons are not used in equal frequency. This phenomenon, termed codon-usage bias has been proposed as a crucial evolutionary mechanism influencing cellular function through its effects on RNA processing, protein translation, and protein folding.  Various organisms and cell types, through this system, are able to coordinate physiological pathways to respond to a variety of stress or growth conditions.  Examine the biochemical, genetic, and evolutionary mechanisms by which codon bias is exploited by the cell to control gene expression.

Recommended Courses:  Genetics (BIOL240) or Cell Biology (BIOL280)

Suggested reading: 

  • Dauna, Z. E., and Kimchi-Sarfaty, C. (2011). Understanding the contribution of synonymous mutations to human disease. Nature Reviews Genetics, 12, 683-691.
  • Hia, F., and Takeuchi, O. (2021). The effects of codon bias and optimality on mRNA and protein regulation. Cellular and Molecular Life Sciences, 78:1909-1928.
  • Iriarte, A, Lamolle, G., and Musto, H. (2021). Codon usage bias: an endless tale. Journal of molecular evolution, 89:589-593.

8. Regulation of Metabolic Rate (Rand, Fall/Winter only)

The ability to alter or regulate metabolic rate (MR) is important for animal survival when resources may be scarce. Several species of endotherms, especially smaller mammals and birds, can enter a torpid or hibernation state that is characterized by an active, physiologically regulated reduction in MR followed by a progressive decrease in body temperature. This allows the organism to reduce the high energy expenditure used to maintain a high body temperature.  Active increases or decreases in MR are regulated by the endocrine and neuronal systems, but ultimately involve subcellular mechanisms that may include the activity of proteins such as glucose transporters, uncoupling proteins, and/or Ca++ATPases. Choose a model system and review the literature to explain the physiological and subcellular mechanisms involved with decreasing and increasing MR.

Recommended courses: Integrative Animal Physiology, Ecological Physiology, or Human Physiology; Cell Biology, Neurobiology, or Biochemistry would be helpful depending on chosen approach.

Suggested reading: 

  • Ali, R.S., M.F. Dick, S. Muhammad, D. Sarver, L. Hou, G.W. Wong and K.C. Welch Jr. (2020) Glucose transporter expression and regulation following a fast in the ruby-throated hummingbird, Archilochus colubris. J. Exp. Biol. 223,1-11. jeb229989. doi:10.1242/jeb.229989
  • Diedrich, V., E. Haugg, C. Dreler and A. Herwig (2020) What can seasonal models teach us about energy balance? J. Endocrinol. 244: R17-R32.
  • Giroud, S., C. Habold, R.F. Nespolo, C. Mejías, J. Terrien, S.M. Logan, R.H. Henning and K.B. Storey (2021) The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms.  Front. Physiol. 11: 1-24. doi: 10.3389/fphys.2020.623665
  • Takahashi, T.M., G.A. Sunagawa, S. Soya, M. Abe, K. Sakurai, K. Ishikawa, M. Yanagisawa, H. Hama, E. Hasegawa, A. Miyawaki, K. Sakimura, M. Takahashi, T. Sakurai (2020) A discrete neuronal circuit induces a hibernation-like state in rodents. Nature 583(7814):109-114. doi: 10.1038/s41586-020-2163-6. Epub 2020 Jun 11.

9. Ecological Mismatch due to Climate Change (McKone Fall/Winter, Hernández Winter/Spring)

Ecological interactions between species require that they be active at the same time and place.  But climate change is rapidly altering the spatial distribution of species as well as the timing of their activities across the seasons.  Novel interactions can result if new species come into contact; alternatively, previously common interactions might be lost due to a spatial or temporal mismatch.  Explore how such changes are altering coevolved ecological interactions in contemporary communities.

Recommended courses:

Population Ecology, Ecosystem Ecology, or Landscape Ecology

Suggested reading:

  • Gérard, M., M. Vanderplanck, T. Wood, and D. Michez. 2020. Global warming and plant – pollinator mismatches. Emerging Topics in Life Sciences 4:77–86.
  • Horton, K. G., F. A. La Sorte, D. Sheldon, T. Y. Lin, K. Winner, G. Bernstein, S. Maji, et al. 2020. Phenology of nocturnal avian migration has shifted at the continental scale. Nature Climate Change 10:63–68.
  • Renner, S. S., and C. M. Zohner. 2018. Climate change and phenological mismatch in trophic interactions among plants, insects, and vertebrates. Annual Review of Ecology, Evolution, and Systematics 49:165–182.
  • Shepard, I. D., S. A. Wissinger, Z. T. Wood, and H. S. Greig. 2022. Predators balance consequences of climate-change-induced habitat shifts for range-shifting and resident species. Journal of Animal Ecology 91:334–344.