Redox Biology in Molecular Signaling

Participants: Alexander, Bierbach, Daniel, Deora, Dos Santos, Furdui, Hollis, Howlett, Kim-Shapiro, King, Lowther, Marrs, Molina, Muday, Nelson, Newman, Petrovic, Poole, Salsbury, Tsang, Turkett, Welker, Zhang

Questions: Redox biology represents a growing area of research worldwide, and refers to the chemical transformations (oxidations and reductions, also referred to as electron transfer reactions) occurring as part of many of the processes essential to all living organisms.  Furthermore, alteration of redox homeostasis underlies many physiological processes and pathological conditions impacting human health. Researchers in this group use chemical biology (utilizing synthetic probes to discover modification sites in cells), structural biology (analyzing protein conformation and dynamics), and cellular imaging (mapping locations of modified proteins in cells) to detect “when and where” particular regulatory modifications take place in proteins and cells, and how redox modifications on proteins change their shapes and functions.  Areas of research focus include the chemical biology of oxygen-, nitrogen- and sulfur-linked modifications, structures and dynamics of metabolic, signaling and repair proteins, and the structure and function of disease-linked proteins emphasizing cancer, diabetes and aging.

Technology: Technology development is a key component of current research in this group; researchers in redox biology design, synthesize, and test chemical probes that are used within cells to track protein oxidation sites. Analyses using these probes provide a wide range of information about protein chemistry, structure, and dynamics and require a research environment rich in high-end instrumentation, including imaging, high resolution mass spectrometry (MS), nuclear magnetic resonance spectroscopy, and X-ray crystallography.  Facilities exist at WFU to support these activities, particularly within the Center for Structural Biology and the Biology, Biochemistry and Chemistry departments.

Emphasis Group Activities: Over the years, regular meetings of members of this group have taken place, initially between experimental and computational investigators of this and the Computational network group (initiated by Fetrow and Poole), and later as a monthly working group discussing active research from one of the members; emphasizing new technologies, computational approaches and  their application in biology and medicine; trouble shooting experimental approaches.  Emerging from these activities was a proposal for a Wake Forest School of Medicine-supported Center focusing in this area, and on July 1, 2016, the new Center for Redox Biology and Medicine (CRBM) was launched, with CMS members Furdui and Poole serving as Co-Directors. The Redox Retreat held annually in May and other bridge activities such as seminars and workshops, and support for pilot studies within the areas of redox will continue, co-sponsored by CMS and the new CRBM.

Implications: When effective communication networks between cells and their extracellular matrix begin to break down, tissue structures are damaged and disease can ensue.  Environmental exposure to various chemicals can also change the normal redox balance of cellular molecules.  Thus, the better we can understand the underlying normal biological processes in cells, the better we can piece together what can go wrong when environments change.