CAREER: Dissecting the Biological Impact of Stem Cell Fusion; a Unified Plan for Stem Cell Discovery via Accessible Engineering

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5) 0844537 Ogle This CAREER project is built on the PI's ultimate research vision to develop accessible technologies to address significant challenges limiting stem cell discovery. The significant challenge addressed is unraveling the mechanism(s) by which stem cells fuse with mature cells and the impact (beneficial or detrimental) of such an event. Fusion of stem cells with mature cells is a regulated process capable of promoting cell survival and differentiation and thus could be of central importance for development, repair of tissues and even the pathogenesis of disease. Given the potential impact, it is surprising that basic aspects of stem cell fusion are unknown including the signals that trigger fusion, the cell surface proteins responsible for mediating fusion, the mechanism of reprogramming and the functional capacity of hybrid cells after fusion. Hindering discovery in this area is lack of appropriate technology to 1) identify fusion partners poised to fuse, 2) track fusion products (i.e., hybrid cells) over time and 3) analyze and sort fusion products in a high-throughput manner. The PI has recently developed technologies to accurately identify fusion products immediately after cell fusion and to track fusion products over time both in culture and in living organisms. Here the PI will develop and characterize a new fluidics platform coupled to a multiphoton microscopy system for high-throughput, flow cytometric analysis of large entities such as fusion products (Objective 1). This system will be used together with previously developed technologies to examine the impact of stem cell-mature cell fusion on hybrid cell function (Objective 2). This novel work exemplifies how technology, when appropriately coupled to basic and clinical science, will transform the way stem cells are characterized, analyzed and stimulated. Execution of Objectives 1 and 2 will provide a template to advance the discovery and understanding of stem cell technologies while promoting teaching, training and learning of a wide range of audiences (Objective 3). Despite widespread enthusiasm for stem cell discovery, understanding of the basic mechanisms of the cellular processes of stem cells (i.e., proliferation, adhesion, differentiation) has been limited by archaic analysis methods. Graduate students have been identified as the ideal conduit for merging technology with basic stem cell science and for conveying this knowledge to academic and industrial communities nation-wide. Graduate students will undergo multimodal training to foster an understanding of key engineering concepts related to stem cell discovery and to promote effective teaching and learning practices. Graduate students who undergo this training will have an opportunity to disseminate their new knowledge by planning and executing an outreach program (Summer Science Camp, WiCell Research Institute), to apply their new knowledge in the context of a professional community workshop (UW Stem Cell Technology Collaboratory, cofounded by the PI), and to disseminate and apply their new knowledge via mentoring of underrepresented undergraduate students.