http://hdl.handle.net/1721.1/7589 2017-07-09T18:36:13Z 2017-07-09T18:36:13Z Ellis, Donald Christian http://hdl.handle.net/1721.1/109640 2017-06-07T06:17:35Z 2017-01-01T00:00:00Z

Genetic screens in vivo using the CRISPR/Cas9 system Ellis, Donald Christian An unmet and paramount need in the field of cancer research is to rapidly translate basic biological findings to clinically relevant therapeutics for cancer patients. Recent technological advances have generated many innovative applications to cancer biology and in a short time have yielded a wealth of information about putative vulnerabilities across a range of cancers. The proposed work involves the development of a technique to quickly probe potential cancer-specific vulnerabilities in vivo adopting methods used in genetic screens. By harnessing the information obtained from large datasets in vitro and the utility of cutting-edge endogenous mouse models, the general aim of this work is to create a method that shortens the gap between findings in the lab to viable treatment options for cancer patients. Thesis: S.M., Massachusetts Institute of Technology, Department of Biology, 2017.; Cataloged from PDF version of thesis.; Includes bibliographical references (pages 82-87).

2017-01-01T00:00:00Z Kaplan, Maxwell Bernard http://hdl.handle.net/1721.1/109060 2017-05-13T06:18:23Z 2017-01-01T00:00:00Z

Coral reef soundscapes: spatiotemporal variability and links to species assemblages Kaplan, Maxwell Bernard Coral reefs are biodiverse ecosystems that are at risk of degradation as a result of environmental changes. Reefs are constantly in a state of flux: the resident species assemblages vary considerably in space and time. However, the drivers of this variability are poorly understood. Tracking these changes and studying how coral reefs respond to natural and anthropogenic disturbance can be challenging and costly, particularly for reefs that are located in remote areas. Because many reef animals produce and use sound, recording the ambient soundscape of a reef might be one way to efficiently study these habitats from afar. In this thesis, I develop and apply a suite of acoustics-based tools to characterize the biological and anthropogenic acoustic activity that largely comprises marine soundscapes. First, I investigate links between reef fauna and reef-specific acoustic signatures on coral reefs located in the U.S. Virgin Islands. Second, I compare those findings to a more expansive study that I conducted in Maui, Hawaii, in which the drivers of bioacoustic differences among reefs are explored. Third, I investigate the distances over which sounds of biological origin may travel away from the reef and consider the range within which these acoustic cues might be usable by pelagic larvae in search of a suitable adult habitat. Fourth, I assess the extent to which the presence of vessel noise in shallow-water habitats changes the ambient soundscape. Finally, I present the results of a modeling exercise that questions how ocean noise levels might change over the next two decades as a result of major projected increases in the number and size of and distance traveled by commercial ships. The acoustics-based tools presented here help provide insight into ecosystem function and the extent of human activity in a given habitat. Additionally, these tools can be used to inform an effective regulatory regime to improve coral reef ecosystem management. Thesis: Ph. D., Joint Program in Oceanography/Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Department of Biology; and the Woods Hole Oceanographic Institution), 2017.; Cataloged from PDF version of thesis.; Includes bibliographical references (pages 131-143).

2017-01-01T00:00:00Z Bors, Eleanor Kathleen http://hdl.handle.net/1721.1/109052 2017-05-13T06:18:22Z 2017-01-01T00:00:00Z

Spationtemporal population genomics of marine species : invasion, expansion, and connectivity Bors, Eleanor Kathleen Every genome tells a story. This dissertation contains four such stories, focused on shared themes of marine population dynamics and rapid change, with an emphasis on invasive marine species. Biological invasions are often characterized by a range expansion, during which strong genetic drift is hypothesized to result in decreased genetic diversity with increased distance from the center of the historic range, or the point of invasion. In this dissertation, population genetic and genomic tools are used to approach complex and previously intractable fundamental questions pertaining to the non-equilibrium dynamics of species invasions and rapid range expansions in two invasive marine species: the lionfish, Pterois volitans; and the shrimp, Palaemon macrodactylus. Using thousands of loci sequenced with restriction enzyme associated DNA sequencing in these two systems, this research tests theoretical predictions of the genomic signatures of range expansions. Additionally, the first chapter elucidates patterns of population genetic connectivity for deep-sea invertebrates in the New Zealand region demonstrating intimate relationships between genetics, oceanographic currents, and life history traits. Invasive shrimp results extend our understanding of marine population connectivity to suggest that human-mediated dispersal may be as important - if not more important - than oceanographic and life history considerations in determining genetic connectivity during specific phases of marine invasions. In invasive populations of lionfish, measures of genomic diversity, including a difference between observed and expected heterozygosity, were found to correlate with distance from the point of introduction, even in the absence of spatial metapopulation genetic structure. These results indicate a signal of rapid range expansion. The final study in this dissertation uses an innovative temporal approach to explore observed genomic patterns in the lionfish. In all, this dissertation provides a broad perspective through the study of multiple species undergoing superficially parallel processes that, under more intense scrutiny, are found to be mechanistically unique. It is only through comparative approaches that predictable patterns of population dynamics will emerge. Thesis: Ph. D., Joint Program in Oceanography/Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Department of Biology; and the Woods Hole Oceanographic Institution), 2017.; Cataloged from PDF version of thesis.; Includes bibliographical references.

2017-01-01T00:00:00Z Peterson, Alexis W http://hdl.handle.net/1721.1/108893 2017-05-12T06:20:41Z 2017-01-01T00:00:00Z

Generating single-domain antibodies against fibronectin splice variants Peterson, Alexis W Here, I describe the process of generating single-domain antibodies which bind to splice variants of fibronectin containing EIIIA or EIIIB. Alpacas were immunized with either purified antigen cocktails, or from the ECM of tumor samples, and antibody libraries were generated. Using these libraries to pan against, I selected for VHH which bind to EIIIA and EIIIB. Since these splice variants are upregulated in tumor angiogenesis and are rarely seen elsewhere in adult tissues, antibodies targeting EIIIA or EIIIB may be of use for imaging tumors and metastases. Thesis: S.M., Massachusetts Institute of Technology, Department of Biology, 2017.; Cataloged from PDF version of thesis.; Includes bibliographical references (page 51).

2017-01-01T00:00:00Z