Modulating the skin immune system with physical stimulus (2015–2018)
Abstract:
In this Fellowship I will continue my highly competitive research program in developing topical diagnostic, therapeutic and prophylactic technologies. My program will be expanded by taking a unique research approach by investigating the immunological effect of physical stimulus locally on the skin¿s resident immune system.
Over the course of my research program, I and others have observed that the application of a physical force alone, with a chemical / molecular stimulus or with skin breaching results in rapid cellular changes to localised immune cells. For example, we recently observed in vivo using transgenic mice that within minutes following application of a minimally invasive microbiopsy, the fluorescence significantly diminished from the immune cells localised directly within the application site. Furthermore, no cellular florescence was detected within the microbiopsy tissue.
This rapid change in cellular fluorescence has not been observed before and suggests that physical stimulus has a potential role on modulating the local microenvironment of resident immune cells. Furthermore, it raises concerns on the design and approach of topical diagnostic and drug
delivery technologies. To negate any potential physical effect mechanical cellular extraction may have, I will utilise an image-guided optical bone marrow microbiopsy being developed in my proposed supervisor Assoc. Prof. Charles Lin¿s laboratory at the Wellman Centre for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA. I will adapt the system for soft tissue (skin) extraction in mice and investigate the
influence physical stimulus has on their immune cells. On return to Australia I will establish a comparable optical system translated for clinical use. In particular I will investigate the interaction between physical stimulus and resident leukocytes within healthy and diseased human skin.
