The Cavanagh lab is generally interested in how the specific structure and inherent flexibility of proteins helps them carry out their biological roles.
For a few years and with some success, our main focus has been on proteins involved in bacterial response/protection and the development of infectious disease. These are proteins that enable bacteria survive in difficult circumstances/environments and help them reach their pathogenic potential. The main types of proteins we study are response regulator proteins and transition state regulator proteins. Please see our 'Research' section for a little more information.
We are also very interested in neurodegenerative processes such as Alzheimer's disease. We have been studying the role of the calcium-binding protein calbindin D28K in suppressing the onset of Alzheimer's. Calbindin D28K appears to regulate both the amyloid and neurofibrillary tangle pathologies that define the disease.
Most recently we have been collaborating with the group of Christian Melander here at NC State, in developing small, non-toxic molecules that both inhibit and disperse highly resistant bacterial biofilms. Our compounds are 100% effective against all Gram negative and Gram positive biofilms so far tested. Approximately 80% of all bacterial infections are from bacteria in the biofilm state.
In addition, we have shown these small molecules to have the remarkable property of being able to re-sensitize bacteria to the antibiotics to which they have become resistant. For example when we add our compounds to MRSA (methicillin resistant staphylococcus aureus), the bacteria are suddenly susceptible to methicillin treatment once more.
We use NMR as our big platform technology, but we are pretty well-rounded when it comes to addressing our research problems. We'll try anything. Consequently some sophisticated mass spectrometry is becoming a major player in our work. We employ just about every biophysical technique you can think of and we're pretty decent computational modelers. Of course there is a lot of molecular biology and genetic work being done too and we have recently begun working with Laura Mathies at NC State in developing toxicological screens using C. elegans.
NMR Solution Structure and DNA-binding Model of the DNA-binding Domain of Competence Protein A.Hobbs CA, Bobay BG, Thompson RJ, Perego M, Cavanagh J Mol Biol. 2010 Mar 17.
Synergistic Effects Between Conventional Antibiotics and 2-Aminoimidazole-Derived Antibiofilm Agents. Rogers SA, Huigens RW 3rd, Cavanagh J, Melander C. Antimicrob Agents Chemother. 2010 Mar 8.
Binding site on human immunoglobulin G for the affinity ligand HWRGWV. Yang H, Gurgel PV, Williams DK Jr, Bobay BG, Cavanagh J, Muddiman DC, Carbonell RG.J Mol Recognit. 2010 Jan 4.
Amide isosteres of oroidin: assessment of antibiofilm activity and C. elegans toxicity.Richards JJ, Reyes S, Stowe SD, Tucker AT, Ballard TE, Mathies LD, Cavanagh J, Melander C. J Med Chem. 2009 Aug 13;52(15):4582-5.
Structural characterization of the conformational change in calbindin-D28k upon calcium binding using differential surface modification analyzed by mass spectrometry. Hobbs CA, Deterding LJ, Perera L, Bobay BG, Thompson RJ, Darden TA, Cavanagh J, Tomer KB. Biochemistry. 2009 Sep 15;48(36):8603-14.
Insights into the nature of DNA binding of AbrB-like transcription factors. Sullivan DM, Bobay BG, Kojetin DJ, Thompson RJ, Rance M, Strauch MA, Cavanagh J. Structure . 2008 Nov 12;16(11):1702-13.
Dihydrooroidin: A Marine Natural Product Congener as an Effective Non-Toxic Antifouling Agent in Marine-Based Paints. Melander, C, Moeller, P.D.R., Ballard, T.E., Richards, J.J., Huigens, R.W., and Cavanagh, J. International Biodeterioration and Biodegradation In press
Co-evolving motions at protein-protein interfaces of two-component signaling systems identified by covariance analysis. Szurmant H, Bobay BG, White RA, Sullivan DM, Thompson RJ, Hwa T, Hoch JA, Cavanagh J. Biochemistry Jul 29;47(30):7782-4