Similar to Toll-like receptors (TLR), proteins of the NLR family serve as intracellular pathogen sensors and regulators of immune responses. Invading bacteria such as those causing the plague, tularemia, and food poisoning are detected by NLRs. Some NLRs normally drive inflammatory responses when macrophages are infected by activating transcription factors such as NF-kB and MAPK as well as inducing production of inflammatory proteins like IL-1. They can also promote programmed cell death to help limit infection. Mutations within select NLRs are involved in a number of inflammatory diseases including Crohn’s Disease and Muckle-Wells Syndrome. One project currently seeks to understand NLR regulation. A second project considers a large protein, CIITA. Unlike other NLRs, CIITA is a transcription factor controlling expression of Major Histocompatibility Class (MHC) II genes. MHC II is absolutely critical to the normal functioning of both cellular and humoral immunity. Understandably, CIITA plays a role in multiple disease states ranging from arthritis and immunodeficiency to AIDS and cancer. Utilizing a wide array of molecular, cellular, biochemical, and animal based approaches we are advancing our understanding of the underlying molecular basis for how these proteins work in both health and disease. Previous students (depending on the project and the student’s skills/interest) have performed bioinformatics, cell culture, cloning, eukaryotic cell transfection, flow cytometry, gene expression assays, immunofluorescence microscopy, PCR, protein assays, and tumor growth/rejection studies. Undergraduate researchers will have the opportunity to interact with technical staff as well as postdoctoral and graduate students.