Education & Training
- Ph.D. in Ecology and Evolutionary Biology from Yale University, 2007
- B.S. in Ecology and Evolutionary Biology from Yale University, 2001
Research Interest Summary
Our lab seeks to understand the molecular basis, evolutionary history, and medical relevance of invertebrate allorecognition. Allorecognition is the ability of most encrusting marine invertebrates—animals like corals and sponges—to distinguish between themselves and other members of their species via cell-cell contact. We study allorecognition using the colonial hydroid, Hydractinia, as a model system. In Hydractinia, allorecognition is controlled by two genes, alr1 and alr2. These genes encode cell surface proteins with highly polymorphic extracellular domains. The sequence of these domains predicts whether colonies will fuse or fight with each other. Colonies that match alleles at alr1 and alr2 fuse, while colonies with mismatched alleles fight. My lab is currently focused on answering the following three questions: (1) What is the molecular basis of allorecognition specificity? Using an in vitro assay, we have determined that the alr1 and arl2 proteins are capable of homotypic binding in trans (between opposing cell surfaces) and that this binding is allele-specific. This provides the first plausible biophysical mechanism for how alr1 and alr2 confer each colony with a unique identity. Many questions still remain, however, including figuring out how evolution has managed to create hundreds of alleles each capable of binding only to themselves. (2) What signaling pathways control allorecognition and are they conserved between Hydractinia and humans? Alr1 and alr2 have large cytoplasmic tails with motifs suggesting they may be involved in intracellular signaling to initiate the fuse or fight response. We hypothesize that this signaling pathway may be homologous to pathways present in humans that are involved in immune responses, including anti-graft responses in organ transplantation. Identifying members of this pathway is key to answering this decades-old question. (3) How does autophagy lead to cell death in Hydractinia allorecognition responses? A final, nascent area of research involves characterizing the role of cell death and autophagy in the allorecognition system. Certain genetic combinations of Hydractinia result in a phenotype wherein the colonies initially fuse but subsequently separate via cell death. Preliminary data indicates that this cell death involves autophagy but, curiously, not apoptosis. Understanding the molecular basis of this phenotype, including how autophagy can lead to cell death, is a top priority.
Rosengarten RD and Nicotra ML. 2010. “Model systems of invertebrate allorecognition.” Current Biology. 21(2):R82-92. doi: 10.1016/j.cub.2010.11.061 PMID: 21256442
Rosa SFP, Powell AE, Rosengarten RD, Nicotra ML, Moreno MA, Grimwood J, Lakkis FG, Dellaporta SL, Buss LW. 2010. “Hydractinia allodeterminant alr1 resides in an Immunoglobulin Superfamily-like gene complex.” Current Biology. 20(12):1122-1127. doi: 10.1016/j.cub.2010.04.050 PMID: 20537535 PMCID: PMC2921677
Nicotra ML, Powell AE, Rosengarten RD, Moreno MA, Paquet N, Grimwood J, Lakkis FG, Dellaporta SL, Buss LW. 2009. “A Hypervariable Invertebrate Allodeterminant.” Current Biology. 19(7):583-589.[PubMed] doi: 10.1016/j.cub.2009.02.040. PMID: 19303297 PMCID: PMC2681180.
Powell AE, Nicotra ML, Moreno MA, Lakkis FG, Dellaporta SL, Buss LW. 2007. “Differential effect of allorecognition loci on phenotype of Hydractinia symbiolongicarpus (Cnidaria: Hydrozoa).” Genetics. 177(4):2101–2107. doi: 10.1534/genetics.107.075689 PMID: 17947438 PMCID: PMC2219508
Nicotra ML and Buss LW. 2005. “A test for larval kin aggregations.” The Biological Bulletin. 208(3):157-158. [PubMed] PMID: 15965120