Kirwin Providence (section 10)
1.Determining the mechanism used (by two different species of bacteria) to inhibit proper skin-wound healing. (Project with relevance to Human health or research)
2. Design and use of micro-fabricated devices to aid in studying cell motility. (Project with relevance to Human health or research)
3. Identification of specific algae proteins that mediate the cells adhesion to solid surfaces in aquatic ecosystems. (Project with relevance to Environmental Science)
Background
Wound healing is a complex and necessary event associated with good health. Many genes work in concert to promote tissue repair. Plasminogen Activator Inhibitor Type 1 (PAI-1) is an example of one such gene. For nearly two decades, I have contributed to publications highlighting the role of PAI-1 in the tissue repair process. My labs most recent contribution (student co-authored paper) demonstrates that PAI-1 is required for optimal monolayer wound repair using keratinocytes (skin cell) in a model of tissue injury. Additionally, PAI-1 has been demonstrated to play a role in blood coagulation and metastatic events. These observations suggest that PAI-1 is intricately connected with many aspects of human biology. While the role of PAI-1 in normal wound healing has been demonstrated, much less is known about PAI-1 and its regulation in bacteria-infected wounds. Current research in my lab suggests that Staphylococcus aureus (a Gram-positive, sphere-shaped bacterium) and Enterobacter aerogenes (a Gram-negative, rod-shaped bacterium) utilize distinct mechanism to influence PAI-1 gene expression. This “misregulation” of PAI-1 is associated with the failure of wounds to completely heal. By integrating Cell Biology techniques into the field of Microbiology, we are utilizing an interdisciplinary approach to determine the mechanism used (by two different species of bacteria) to inhibit proper wound healing.
In collaboration with Dr. Toner (Microsystems Bioengineering Facility, Massachusetts General Hospital) we have also designed a novel micro-fabricated devices that we use to study mechanisms associated with cell motility. Micro-fabrication is the process of making items on a miniature scale. Our device (less than 1 square inch in size) allows us to study how specific bacteria metabolites influence the behavior of a specific type of white blood cell called a neutrophils.
Finally, I capitalize on my experiences of studying the interplay between bacteria and mammalian cells to explore how primitive microscopic plant-like cells (algae) adhere to surfaces. Algae share various biochemical characteristics with human immune cells. Adhesion to solid surfaces, for example, is important for both cell types. In collaboration with a local Botanist (Dr. David Domozych), we are asking the question “How do freshwater algae attach to solid surfaces in lakes and streams?” This attachment is important because it facilitates the formation of biofilms. These biofilms are important to aquatic food webs, and has relevance in carbon cycling. Many native species of algae are under predation pressure from non-native invasive species. An understanding of how algae attach to solid surfaces in lakes and streams may contribute to Mitigation Strategies for endangered aquatic ecosystems.
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