1. Ecology of the microbiome in response to change

Anderson (Fall/Winter & Winter/Spring)

The microbiome, or the community of microorganisms inhabiting a specific ecosystem, has become a hot topic as new sequencing technologies and lab techniques have allowed us to better understand the extent of microbial diversity and function. These microbiomes inhabit ecosystems ranging from the human gut to the open ocean to the phyllosphere of plants. When ecosystems change in response to a disturbance or long-term shift, the response of the microbiome can have profound effects on the whole ecosystem. For example, shifts in microbial community structure can change the relative abundances of important metabolites, which can have an impact on host health in the case of human microbiomes, or greenhouse gas emissions in the case of soil microbiomes. Microbial communities can also contribute to feedback loops that can either counteract or amplify a change in the ecosystem. Explore the response of the microbiome (or virome) in response to a shift in a specific ecosystem and the impact that response has on the ecosystem it inhabits.

David, L. et al. (2013) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559-563.

Thurber, R.V. et al. (2009) Metagenomic analysis of stressed coral holobionts. Environmental Microbiology 11(8), 2148-2163.

Mackelprang, R. et al. (2011) Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw. Nature 480, 368-371.

Wilner, D. et al. (2009) Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PLoS ONE 4(10):  e7370.

Koren, O. et al. (2012) Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150(3), 470-480. 

2.  Topics in neural crest cell biology

Jacques-Fricke (Fall/Winter & Winter/Spring)

Neural crest cells are multipotent stem cells that are found in vertebrate embryos. During development, neural crest cells migrate extensively and form a variety of derivatives, including the peripheral nervous system, craniofacial structures, pigment cells in the skin, and the outflow tract of the heart. Developmental dysregulation of neural crest cells underlies several birth defects, and in adulthood, neural crest cell derivatives can become highly metastatic cancers. Because of the unique features of this cell type, research in neural crest cells addresses a variety of biological questions regarding evolution, pluripotency and cell specification, cell motility and migration, and modeling and treatment of diseases and birth defects. For this question, examine one of these topics as it intersects with neural crest biology.

Green, S.A, Simoes-Costa, M., and Bronner, M.E. 2015. Evolution of vertebrates as viewed from the crest. Nature, 520: 474-482.

Simoes-Costa, M., and Bronner, M.E. 2016. Reprogramming of avian neural crest axial identity and cell fate. Science, 352: 1570-1573.

Heuckeroth, R.O., and Schafer, K-H. 2016. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention. Developmental Biology, 417: 188-197.

Scarpa, E., and Mayor, R. 2016. Collective cell migration in development. Journal of Cell Biology, 212: 143-155.

Bronner, M.E., and Simoes-Costa, M. 2016. The neural crest migrating into the 21st century. Current Topics in Developmental Biology, 116: 115-134.

Liu, J.A., and Cheung, M. 2016. Neural crest stem cells and their potential therapeutic applications. Developmental Biology 419: 199-216.

Van Otterloo, E., Williams, T., and Artinger, K.B. 2016. The old and new face of craniofacial research: How animal models inform craniofacial genetic and clinical data. Developmental Biology, 415: 171-187. 

3.  Silent synapses and addiction

Jaramillo (Fall/Winter & Winter/Spring)

Silent synapses are characterized by the presence of NMDA glutamate receptors in the postsynaptic membrane, but no AMPA-type glutamate receptors. Thus, under typical membrane potentials these synapses are silent since at these potentials the NMDA glutamate receptors are blocked. Despite their “silence”, silent synapses have emerged as a significant locus of plasticity in the brain. For example, silent synapse activation in the hippocampus has been implicated in Long-Term Potentiation. Interestingly, it’s been shown that addiction tends to silence synapses in brain reward circuits. Explore the effects of narcotics on silent synapse function in the nucleus accumbens.

Opposing Mechanisms Mediate Morphine- and Cocaine-Induced Generation of Silent Synapses. 19 (7): 915–25. doi:10.1038/nn.4313.

Maturation of Silent Synapses in Amygdala-Accumbens Projection Contributes to Incubation of Cocaine Craving. 16 (11): 1644–51. doi:10.1038/nn.3533.

In Vivo Cocaine Experience Generates Silent Synapses. 63 (1): 40–47. doi:10.1016/j.neuron.2009.06.007. 

4. Diversity in ecological communities

McKone, Hernández, or Hougen-Eitzman (Fall/Winter & Winter/Spring)

Biological diversity often is considered one of the fundamental characteristics of ecological communities, with potential consequences for community properties such as stability, resilience to disturbance, or ecosystem function.  Yet there are many ways that diversity can be defined and measured beyond a simple species count.  Evaluate how different types of diversity measures can be used, and how the choice of metric influences the consequences of diversity for community structure and function.  Potential topics include alpha/beta/gamma diversity, phylogenetic diversity, and genetic diversity within species.

Davies, T.J., M.C. Urban, B. Rayfied, M.W. Cadotte, and P.R. Peres-Neto.  2016.  Deconstructing the relationships between phylogenetic diversity and ecology: a case study on ecosystem functioning.  Ecology 97:2212-2222.

Ehlers, B.K., C.F. Damgaard, and F. Laroche.  2016.  Intraspecific genetic variation and species coexistence in plant communities.  Biology Letters 12:20150853

Fournier, B., A. Mouly, M. Moretti, and F. Gillet.  2017.  Contrasting processes drive alpha and beta taxonomic, functional and phylogenetic diversity of orthopteran communities in grasslands.  Agriculture, Ecosystems & Environment 242:43-52. 

5. Evolution of intersexual conflict

McKone (Fall/Winter & Winter/Spring)

Successful sexual reproduction requires the union of two genomes, usually from different parents.  Fitness of female and male parents are not necessarily maximized in the same way, giving rise to the possibility of intersexual conflict.  Examine the evolutionary causes and consequences of intersexual conflict in reproductive behavior. 

Gavrilets, S.  2014.  Is sexual conflict an “engine of speciation”?  Cold Springs Harbor Perspectives in Biology 6:a017723.

Paquet, M., and P.T. Smiseth.  2015.  Maternal effects as a mechanism for manipulating male care and resolving sexual conflict over care.  Behavioral Ecology  27:685–694.

Pischedda, A., and A.K. Chippindale.  2017.  Direct benefits of choosing a high-fitness mate can offset the indirect costs associated with intralocus sexual conflict.  Evolution 71:13240. 

6. Multiple resource limitation in ecosystems

Hernández (Fall/Winter & Winter/Spring)

Nutrient availability commonly limits ecological processes (such as net primary productivity) in both aquatic and terrestrial ecosystems. While Leibig’s “Law of the Minimum” suggests that ecological processes will be limited by a single resource, recent studies have demonstrated that many ecosystems exhibit resource co-limitation. Examine the drivers and consequences of multiple resource limitation in a specific ecosystem.

Bracken, M.E.S., H. Hillebrand, E.T. Borer, et al. 2014. Signatures of nutrient limitation and co-limitation: responses of autotroph internal nutrient concentrations to nitrogen and phosphorus additions. Oikos 124: 113-121.

Fay, P.A., S.M., Prober, W.S. Harpole, et al. 2015. Grassland productivity is limited by multiple nutrients. Nature Plants 1: 15080.

Moore, C.M., M.M. Mills, K.R. Arrigo et al. 2013. Processes and patterns of oceanic nutrient limitation. Nature Geoscience 6: 701-710.

Saito, M.A., M.R. Ilvin, D.M Moran, et al. 2014. Multiple nutrient stresses at intersecting Pacific Ocean biomes detected by protein biomarkers. Science 345: 1173-1177.

Wurzburger, N. and S.J. Wright. 2015. Fine root responses to fertilization reveal multiple nutrient limitation in a lowland tropical forest. Ecology 96: 2137-2146. 

7.  The unexpected roles of granulocytes in immunity

Walser-Kuntz (Fall/Winter & Winter/Spring)

The granulocytes of the innate immune system – basophils, eosinophils, and neutrophils – have not been as well studied as B and T cells, yet they play important and sometimes unexpected roles in immunity. For example, recent findings show that in addition to phagocytosis, neutrophils are able to destroy microbes by releasing NETs, complex structures composed of antimicrobial proteins and histones. Eosinophils, well known for their role in anti-helminth defense and asthma, are now understood to help regulate metabolism and inflammation in adipose tissue. The least understood granulocyte is the basophil; basophils are protective in tick and helminth immunity, but more recently have been shown to play a detrimental role in cancer and allergy. Explore the current understanding of the activation and response of one of these granulocyte subsets in either a typical immune response or during an autoinflammatory condition, making sure to include the role of cell-cell communication and cell signaling.

Rivera A, et al. 2016. Innate cell communication kick-starts pathogen-specific immunity. Nature Immunology 17(4); 356-363. Nat Immunol. 2016 Mar 22; 17(4): 356–363.

Steiner M, et al. 2016. The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions. Biomed. Res. Int. 2016:1-16.

Thieblemont, N, et al. 2016. Human neutrophils in auto-immunity. Seminars in Immunology 28 (2): 159–173.

Withers S, et al. 2017. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality Scientific Reports 7, Article number: 44571 doi:10.1038/srep44571.

Geering, B, et al. 2013. Living and dying for inflammation: neutrophils, eosinophils, basophils. Trends in Immunology 34: 398–409.

Brinkmann V, et al. 2012. Neutrophil extracellular traps: Is immunity the second function of chromatin? Journal of Cell Biology 198 (5): 773. 

8.  Stem cells and their niches 

Wolff (Fall/Winter & Winter/Spring)

Stem cells have remarkable properties of self-renewal and potential to produce differentiated cells during development or for adult tissue maintenance and repair. Stem cell therapies provide great promise for regenerative medicine, with embryonic (ESCs) and induced pluripotent stem cells (iPSCs) emerging in the past decade as a potential source of personalized “replacement” cells for injured tissue. Damage or deterioration to stem cell populations in embryos and adults is associated with pathogenesis. 

Fate and function of stem cells depends not only on their intrinsic properties, but also on extrinsic cues that come from the closely associated cells that comprise their stem cell niche.  Stem cell niches are conserved among multicellular organisms, and provide both supportive and instructive signals that influence survival, renewal, and differentiation of the stem cells in their care.  Innovations in methods that recapitulate the niche in three-dimensional culture have made possible the in vitro development of stem cells into embryoids and organoids for research and potential therapies.

Explore the role of signaling from a stem cell niche (or niches) in the development, homeostasis, and/or pathogenesis of a cell, tissue, or organ.   

NIH Stem Cell Basics:  https://stemcells.nih.gov/info/basics/1.htm

Llorens-Bobadilla, E., and Martin-Villalba, A. (2017). Adult NSC diversity and plasticity: the role of the niche. Curr Opin Neurobiol 42, 68–74.

Moore, K.A., and Lemischka, I.R. (2006). Stem cells and their niches. Science 311, 1880–1885.

Murrow, L.M., Weber, R.J., and Gartner, Z.J. (2017). Dissecting the stem cell niche with organoid models: an engineering-based approach. Development 144, 998–1007.

Plaks, V., Kong, N., and Werb, Z. (2015). The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells? Stem Cell 16, 225–238.