The oxidation-reduction (redox) reactions occurring in the cells and tissues of our body are essential to their proper function and have implications in aging and many diseases, including cancer. Many therapies and foods have anti-oxidant properties, but researchers have an incomplete understanding of how they might affect our cells and bodies. The aim of the project is to develop new nanotechnologies to improve the measurement of redox phenomena in cells and organisms to give a better picture of how they relate to health and disease. The principal investigator's laboratory is developing these capabilities by studying new materials with unique properties that may have big impact on many fields. Scientists, students, entrepreneurs, and even artists will work together to teach the public about these materials, make new discoveries about them, and to make them available to more people than ever before.
A growing body of work in the field of cellular metabolism has shown that many fundamental biological processes are under the control of redox chemistry. Changes in redox phenomena are also implicated in many diseases, including cancer. The role of reactive species in cancer cell signaling and survival is not well-understood, however, including the roles of pro- and anti-oxidants. A large effort has started to present the basic metabolic and energetic abnormalities of cancer as a new hallmark which defines the disease. Still, the understanding of the connections between the genetic alterations in signaling pathways and the resulting complex phenotypic output of metabolism and bioenergetic changes is cursory. Current options for making redox measurements in biology fall short of the unique needs of the field. The quantification of redox potentials in living tissues would allow for measurements to be compared accurately between different laboratories. A tool sensitive to redox potentials in the cellular environment across the wider physiologic range would give researchers access to more testable hypothesis. Many fields, including diagnostics, process engineering, chemical product testing and safety, drug screening, and drug development could also benefit from the ability to measure or transmit electrochemical signals optically. In this project, the PI will develop a new class of optical reporters to measure the full-range redox potential quantitatively in live cells and organisms. The overall objective of this application is to translate the wide intrinsic voltage sensitivity and emission response of photoluminescent carbon nanotubes into biological systems. Nanotubes will be engineered for specific sensitivity across the physiologic range using new covalent and non-covalent functionalization methods to modulate nanotube emission. This approach will develop new capabilities to understand and control the near-infrared optical response of nanotubes within biological environments, as well as to modulate biological interactions of these materials to target specific sub-cellular compartments. These sensors will be used to interrogate redox landscapes in normal and diseased states, including Kras-mutant tumors. To assist with the development and dissemination of the research materials, and to teach the public about these new materials and findings with them, several initiatives are going to be implemented. The principal investigator designed a bioengineering research project to be conducted in a STEM-focused charter high school to develop methods to modulate the long-term biocompatibility of carbon nanotube sensors. The principal investigator is also working with a resident artist to use carbon nanotube-based 'nanopaints' to both educate the public and improve the availability of research materials for the nano/bioscience/art communities. A new undergraduate engineering summer program will be initiated to give engineering students the experience of working in a cancer research setting while giving faculty and trainees access to students with engineering backgrounds.