BME PhD Prospectus Defense - Yasha Sharma

10:00 am on Wednesday, July 10, 2013
44 Cummington St, Room 401
Title: “Collective Behavior of Mammalian Cells in 3-Dimensional Matrices”

Muhammad Zaman (Chair, Advisor), BME, BU
Michael Smith, BME, BU
Matt Nugent, Opthalmology and BME, BU
Roger Kamm, Mech E., MIT

Cell migration is known to be crucial in critical functions of biology: wound healing, angiogenesis, development, and cancer motility and invasion. It has been extensively characterized for single cells in physiological and clinical contexts as well as in in vitro and computational models. Collective cell migration, however, despite being a hallmark process as well as the predominant mode of tissue invasion in epithelial cancers, is yet to be analyzed and characterized as thoroughly. Collective motion is now believed to be governed by the same set of fundamental laws in vastly unrelated systems--birds, fish, locusts, bacteria, and human crowds. All of these systems self-organize to behave as ‘larger than the sum of their parts’, displaying behavior rarely seen otherwise. Collective migration of cells has been observed in a variety of systems, from 2D sheets in wound healing, to branching morphogenesis in mammary glands, to clusters in cancer invasions. All of these systems are believed to have either temporary or permanent specialized ‘leader cells’ which are responsible for movement of the collective. In cancer, leader cells are highly invasive and motile cells that may either be permanently or temporarily specialized. Even a small number of such cells can impart high invasive potential to tumors that would not otherwise be invasive. While some research has characterized biological properties of leader cells, currently, there is no good quantitative method to predict and identify leader cells. In this research, collective cell migration will be studied in vitro. Leader cells will be identified from live-cell imaging data, and their dynamic properties will be characterized. Synthesis of data collected into a computational model will inform further experiments to characterize collective migration. This research will bridge the gap between current studies of collective migration at the cellular and molecular level with those at the systems level that study interactions between cells, density dependent phases, and the emergence of collective properties. It will identify the essential mechanisms to collective migration and invasion in epithelial derived cancer, thus providing crucial information to cancer treatment and therapeutic research.