Research Interest/Area of Expertise
post-transcriptional gene regulation by non-coding RNAs; RNA-protein interactions; RNA folding thermodynamics of structural rearrangements
Clostridium difficile; mechanisms of action of large clostridial toxins, toxin inhibition, re-engineering of clostridial toxins for cellular delivery
STEM Education: understanding barriers to the adoption of evidence-based instructional practices by STEM faculty; intervnetions to improve retention of underrepresented groups in STEM; adoption of course-based undergraduate research experieces (CURES)
Our laboratory is interested in biological molecules that structurally rearrange as part of their normal activity.
Non-coding RNAs and the proteins with which they interact. Non-coding RNAs (ncRNAs) are involved in a variety of regulatory processes associated with mRNA stability and post-transcriptional gene regulation. We are using a variety of methodologies including structure mapping, CD spectroscopy, fluorescence, and microcalorimetry to probe the structural changes associated with the biology of ncRNAs. One system under study is DsrA, a ncRNA from E. coli involved in the cold shock response. Together with Hfq (Figure 1), a bacterial homolog of the Sm- and Lsm proteins, DsrA regulates RpoS translation. We have probed the different faces of Hfq and shown that they both bind RNAs but with different specificities. Hfq also interacts with a variety of proteins. We are looking at the way in which the RNAs bound to Hfq help to specify the protein components in this dynamic RNA-protein particle.
Thermodynamics of RNA Folding. RNA folding and RNA structural rearrangements are important determinants of the biological activity. We use CD, isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) to probe these structural changes and the fundamental thermodynamics of RNA folding transitions. We have been looking extensively at heat capacity changes (ΔCP), the temperature dependence of the ΔH. We are exploring the fundamental properties of this thermodynamic parameter, such as its physical origin in RNA folding, its dependence on oligonucleotide length and sequence, its dependence on ion condensation and water interactions, and the way it responds to divalent ion binding. We have found that the ΔCP can be used, among other things, to reveal information about the residual structures in the “unfolded” state. Such structures have a major impact on isothermal folding.
Mechanistic Analysis of the Large Clostridial Cytotoxins. The laboratory is also investigating the mechanistic enzymology and biophysics of toxins A and B from Clostridium difficile, a common enteric bacterium. Infection with this organism is the primary cause of antibiotic-associated diarrhea (a condition that afflicts >3 million patients annually). Toxins A and B catalyze mono-glucosylation of the RhoA sub-family of small G-proteins, inducing apoptosis in the afflicted cells. We have cloned and expressed both the 66kD glucosyltransferase domain as well as the intact 300 kD holotoxin. We are using these materials to explore structural transitions required for translocation across cellular membranes during pathogenesis and substrate recognition.
STEM Education: Education work focuses on the barriers for facutly to adopt evidence-based pedagogies in their classrooms. We work on multiple levels. Through new faculty workshops, we help faculty learn about these techniques before they develop their own teaching style. Through workshops on campus we help faculty at all levels understand what these techniques are and how one can implement them effectively in the classroom. Through the management of a faculty learning community, we support teams of faculty interested in the adoption and who wish to learn together with new adopters. The SSTEPs fellows program helps provide resources that buy faculty the time necessary to implement these reforms. Additional support for student-based pedagogies is available through a Learning assistants (LA) program that provides mentors in the classroom for teams working on in class exercises.
Diversity Programs: ReBUILDetroit is a multicenter program focused on improving diversity in the biomedical research enterprise.
Figure 1. Hfq hexamerizes to form a very stable toroidal structure. The top and bottom faces both bind RNAs but the sites have different specificities and functions.
Education – Degrees, Licenses, Certifications
- B.S. Yale University 1990
- Ph.D. MIT, 1995
- Post-Doctoral Fellowship, 1995-1999, Univ. of Colorado, Boulder
Awards and Grants
NSF-IUSE (PI): (DUE-1524878) WSU-Student Success Through Evidence-Based Pedagogies 8/1/15 – 7/31/20 $2,995,000
NSF-WIDER (PI): (DUE-1347576) WSU-Widening Implementation and Dissemination of Evidence-based Reoforms. 9/15/13 – 1/31/16 $250,000
NSF-CHE (CHE-1306063) Protein Translocation Using Chimeric Toxins (PI) 7/15/13 – 5/31/17 $400,000
Research Corporation for Science Advancement (PI) Cottrell Scholars Collaborative – New Faculty Workshops in Chemistry
10/01/12 - 09/30/17 $45,000
NIH - WSU-BEST (Broadening Experiences for Scientific Training) (PI – Mathur) 9/20/13 – 8/19/18 $1,800,000
NIH DPC (Director, Research Enrichment Core): Research Enhancement for BUILDing Detroit (Director, PI – Gary Kuleck) 9/1/14 – 8/31/19 $21,435,853
2017 RNA Society, Lifetime Service Award
2015 Michigan Distinguished Professor of the Year
2013 Wayne State University, President’s Award for Teaching Excellence
2012 Wayne State University, College of Liberal Arts and Sciences Teaching Award
2008 Wayne State University, Career Development Award
2007 Wayne State University, Faculty Mentoring Award,
2002 Cottrell Scholar of Research Corporation
1995 NSF Post-doctoral Research Fellowship in Chemistry
1986 Westinghouse Science Talent Search Scholarship
Meyers, F.J., Mathur, A, Fuhrmann, CN, O’Brien, TC, Wefes, I, Labosky, PA, Duncan, DS, August, A, Feig, A, Gould, KL, Friedlander, MJ, Schaffer, CB, Wart, AV and Chalkley, R, (2016) The origin and implementation of the Broadening Experiences in Scientific Training programs: an NIH common fund initiative. FASEB J. 30, 507-514.
Feig, AL Ed. (2016) Methods in Enzymology - Microcalorimetry.Vol. 567. doi: 10.1016/S0076-6879(15)00652-7
Cowardin CA, Jackman BM, Noor Z, Burgess SL, Feig AL, Petri WA Jr. (2016) Glucosylation Drives the Innate Inflammatory Response to Clostridium difficile Toxin A, Infect Immun. 2016 Jul 21;84, 2317-23. doi: 10.1128/IAI.00327-16
Bradforth SE, Miller ER, Dichtel WR, Leibovich AK, Feig AL, Martin JD, Bjorkman KS, Schultz ZD, Smith TL. (2015) University learning: Improve undergraduate science education. Nature 523(7560):282-4. doi: 10.1038/523282a
Feig AL.(2015) Reflections on 20 years of RNA science. RNA 21(4):609-10. doi: 10.1261/rna.050542.115
Mundigala H, Michaux JB, Feig AL, Ennifar E, Rueda D. (2014) HIV-1 DIS stem loop forms an obligatory bent kissing intermediate in the dimerization pathway. Nucleic Acids Res. 42(11):7281-9. doi: 10.1093/nar/gku332
Faner MA, Feig AL. (2013) Identifying and characterizing Hfq-RNA interactions.Methods. 63(2):144-59. doi: 10.1016/j.ymeth.2013.04.023.
Swett, R., Cisneros, G. A., Feig, A. L. (2012) Conformational Analysis of Clostridium difficile Toxin B and its Implications for Substrate Recognition. PLOS One. 7(7): e41518. doi:10.1371/journal.pone.0041518
Kern, S. M. and Feig, A. L. (2011) Adaptation of Clostridium difficile toxin A for use as a protein translocation system. Biochem. Biophys. Res. Commun.405(4) 570-574. doi:10.1016/j.bbrc.2011.01.070.
Abdeen, S. J., Swett, R. J., and Feig, A. L. (2010) Peptide inhibitors targeting Clostridium difficile toxins A and B, ACS Chem Biol 5, 1097-1103.
Salim, N.N., Faner, M.A., Philip, J., and Feig, A. L. (2012) Requirement of Upstream Hfq Binding (ARN)x Elements in glmS and the Hfq C-Terminal Region for GlmS Up-regulation by sRNAs GlmZ and GlmY. Nucl. Acids Res. 40, 8021-32. doi:10.1093/nar/gks392
Salim, N. Lamichhane, Zhao, R. Banerjee, T. R. Rueda, D and Feig, AL. (2012) Thermodynamic and Kinetic
Analysis of an RNA Kissing Interaction and its Resolution into an Extended Duplex. Biophys. J.102, 1097-1107. doi:10.1016/j.bpj.2011.12.052
Salim NN, Feig AL. (2010) An upstream Hfq binding site in the fhlA mRNA leader region facilitates the OxyS-fhlA interaction. PLoS One. 2010 Sep 28;5(9). pii: e13028. PMID: 20927406
Mikulecky, PJ and Feig, AL. (2006) Heat Capacity Changes Associated with Nucleic Acid Folding. Biopolymers, 82, 38-58.
Winter 2017: CHM6635/CHM7635 - Tools of Molecualr Biology
UGR1050 - Research Methods