This proposal seeks funding for the Center for Biophotonics Sensors and Systems (CBSS) located at the University of California, Davis (UC-D). Funding Requests for Fundamental Research are authorized by an NSF approved solicitation, NSF 11-570. The solicitation invites I/UCRCs to submit proposals for support of industry-defined fundamental research.
Tumor resistance to anti-cancer therapy is a major obstacle to further improving cancer patient survival. Accumulating experimental and clinical data suggest that cancer stem cells (CSCs), which comprise less than 1% of total tumor cells, are able to self-renew and are responsible for the aggressive phenotype of many human cancers. There is an unmet need in elucidating the unique features of cancer stem cells. Identification of the markers that best delineate this population of cells is essential to develop more effective cancer treatment. This proposed study will detect the development and evolution of these markers in CSC-enriched cancer cell populations to better identify cells responsible for tumor resistance to anti-cancer therapy and tumor metastasis and to understand cancer cell proliferation. This project proposes to demonstrate the application of novel cellular labels based on surface enhanced Raman scattering (SERS) for monitoring CSC development during cell division.
If successful, the proposed project will be able to trace the dynamic alterations of a CSC to address many unanswered questions about how these cells proliferate. This information will be important for future development of targeted therapies to inhibit cancer growth and ultimately enhance patient survival. The industry support of the I/UCRC and its active participation in this research project enhances the graduate educational experience by providing a pipeline for talented engineers and scientist to industry.. UC Davis' commitment to develop the academic potential of underrepresented groups in STEM fields will be further enhanced by offering industrial career options, informal mentorships and internships with its I/UCRC partners. The close interaction with the industry partner (BD Biosciences) will lead to the development of new biomedical technology of immediate relevance to the company. Application of this technology specifically to breast cancer stem cell research will have a major impact in the understanding of the molecular mechanisms of the disease, which will impact the discovery of new treatments.
Understanding the inner workings of single biological cells is extremely important to unravel the mechanisms behind the development of many diseases. Optical imaging is a very powerful approach to study cells, providing the ability to visualize the structure and function of cells at unprecedented resolutions and speeds. The images of cells analyzed under an optical microscope are often enhanced by using fluorescent labels that target specific regions of the cells. However, the properties of these labels are imperfect; their signal fades away over time and there are limits to the number of labels that can be detected simultaneously. Both of these issues make it difficult to study the complex biochemistry involved in cell behavior. The research supported by this award was designed to investigate the properties of a new type of cell label based on gold metallic nanoparticles that provides a potential solution to the problems mentioned above. The results of our experiments showed that the brightness of these new nanoparticle labels are sufficient for imaging live cells and that they can be used to target specific regions of a cell. We have developed two different labels that target two different proteins on the surface of a cell. With these labels, we have demonstrated the ability to image the biochemistry of a single cell over a 24 hour period, which is not possible with current fluorescent labels. The results of this project show the promising potential of using these new labels for cell analysis, which opens up tremendous new opportunities to study cell behavior. Also, because this award was intended to support industry-defined fundamental research, we have worked very closely with an industry partner who is interested in developing these new labels for cell analysis. In addition, this project helped broaden participation of groups that are underrepresented in the physical sciences. It was used as a tool to train two early-career female scientists in multidisciplinary research combining the fields of biophotonics and cell biology. The project also supported an undergraduate, female student from an underrepresented minority group seeking to gain experience in cutting edge research.
