- The Pennsylvania State University, Dept. of Biochemistry & Molecular Biology Associate Head for Graduate Education (2018 – present)
- The Pennsylvania State University, Dept. of Biochemistry & Molecular Biology Professor of Biochemistry & Molecular Biology (2015 – present)
- The Pennsylvania State University, Dept. of Biochemistry & Molecular Biology Associate Professor of Biochemistry & Molecular Biology (2008 – 2015)
- The Pennsylvania State University, Dept. of Biochemistry & Molecular Biology Assistant Professor of Biochemistry & Molecular Biology (2002 – 2008)
- DOE-EnergyBiosciences Research Fellow of the Life Sciences Research Foundation, Stanford University Medical School (1997-2002)
- Human Frontier Science Program Long-Term Fellow, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch, France (1996-1997)
- Ph.D. in Biology, Massachusetts Institute of Technology (1995)
- M. S. in Biology, Stanford University (1989)
- B.S. in Chemistry and Biology (honors and distinction), Stanford University (1989)
Departmental of University Committees
- Member, BMB Department Head Search Committee (2007-2008)
- Member, University AD14 Review Committee of College of Science Dean (2008-2009)
- Member College of Science Preprofessional Evaluation Committee (2009-present)
- Member, Penn State MD/Ph.D. Steering Committee (2010-2017)
- Member, Automated Biological Calorimetry Facility Advisory Committee (2011-2014)
- Member, College of Science Sabbatical Leave Committee (2012)
- Member, Paul Berg Award Selection Committee (2012)
- Member, Center for Excellence in Science Education (2012-present)
- Member, Undergraduate Education Advisory Committee (2012-2013)
- Penn State Faculty Senate (2013-present) Member, Senate Committee on Faculty Affairs (2013-2015)
- Member, Senate Committee on Curricular Affairs (2015-present)
- Curricular Representative, College of Science (2015-present)
- Member, University Committee on Assessment of Learning (2016-2018)
- Member, College of Science Undergraduate Research Advisory Council (2017-present)
- Chair, Subcommittee on Writing Across the Curriculum (2018-present)
- Director, Beckman Scholars Program at Penn State (2019-present)
- Member, C.I. Noll and College Faculty Awards Committee (2019-present)
- Department Committees Member, Marker Lecture Selection Committee (2002-2004)
- Chair, Marker Lecture Selection Committee (2004-2005)
- Participant, BMB Strategic Plan Committee (2004)
- Member, BMB Faculty Search Committee (2004)
- Member, BMMB Graduate Affairs Committee (2005-2009)
- Member, IBIOS Candidacy Exam Committee (2006-2007)
- Chair, BMB Honors and Awards Committee (2008-2009)
- Member, BMB Promotion and Tenure Committee (2009-2010)
- Member, BMB Instructional Faculty Evaluation Committee (2009-2011)
- Member, BMMB Candidacy Committee (2010-2011)
- Member, BMB Undergraduate Affairs Committee (2012-2015; 2017-2018)
- Member, BMB Undergraduate Program Assessment Committee (2013-2015)
- Member, BMB Peer Teaching Evaluation Committee (2014-2017)
- Chair, BMB Junior Faculty Mentoring Committee (2015-2017)
- Kenneth C. Keiler - 21 - Organizer, BMB Junior Faculty Grant Application Review Panel (2015-2017)
- Chair, BMB Peer Teaching Evaluation Committee (2017-2018)
- Chair, BMMB Graduate Program Steering Committee (2018-present)
- Chair, BMMB Graduate Program Admissions and Recruiting Committee (2018-present)
Program or Department Affiliations
|The BMMB Graduate Program||Molecular, Cellular, and Integrative Biosciences|
|Center for RNA Molecular Biology|
Protein quality control and new antibiotics
Our mission is to understand how protein quality control is maintained during stress responses and homeostasis by trans-translation and alternative pathways. Our goal is to characterize the fundamental biochemistry, genetics, and cell biology of these systems, and to use this knowledge to develop antibiotics and tools for basic research.
How do cells ensure protein quality and maintain protein synthesis capacity?
There are a wide variety of errors that can occur during transcription and translation, and cells must have mechanisms to ameliorate the deleterious effects of these errors in order to maintain optimal fitness. In bacteria, problems during transcription or translation frequently lead to a ribosome that reads to the 3’ end of an mRNA without terminating translation at a stop codon. To deal with these “non-stop” translation complexes, bacteria have a pathway known as trans-translation. During trans-translation, tmRNA, a specialized RNA molecule, and SmpB, a small protein, recognize a non-stop translation complex and use a short reading frame within tmRNA to release the ribosome and promote degradation of the nascent polypeptide. Genes encoding tmRNA and SmpB have been identified in >99% of sequenced bacterial genomes, suggesting that trans-translation confers a strong selective advantage in most environments that support bacterial life. In fact, trans-translation is essential in many bacteria. Species in which tmRNA can be deleted have a backup system that can perform similar functions, albeit less efficiently.
New antibiotics. Recently, our identification of small-molecule inhibitors of trans-translation has opened new opportunities for translational research and basic science. We identified and characterized inhibitors of trans-translation, and showed they have broad-spectrum antibiotic activity. We have several projects to advance drug development with these compounds.
The inhibitors we identified also provide new tools to understand the role of trans-translation in bacterial physiology and genetics. We are using these inhibitors to examine the physiological response of bacteria to losing trans-translation activity, and for chemical genetic experiments to understand why trans-translation is universally conserved in bacteria.
Our experience with inhibitors of trans-translation led us to explore other pathways that are candidate targets for antibiotic development and chemical biology studies. In collaboration with Sarah Ades (Penn State), we engineered and validated assays for inhibition of two mechanisms that are important for maintenance of the cell envelope in Gram-negative bacteria: αE-directed transcription, and Hfq-sRNA repression of gene expression.
Honors and Awards
- 20012 - 2013, Tombros Faculty Fellowship, Penn State University
- 2014, Tershak Teaching Award, Penn State University
- 2015, C. I. Noll Award for Teaching Excellence, Eberly College of Science and Eberly College of Science Alumni Society
- 2018 - Present, Fellow, American Academy of Microbiology
- Goralski TDP, Kirimanjeswara GS, Keiler KC (2018) “A new mechanism for ribosome rescue can recruit RF1 or RF2 to nonstop ribosomes.” mBio 9:e02436-18.
- Simonson AW, Lawanprasert A, Goralski TDP, Keiler KC, Medina SH (2018) “Bioresponsive peptide-polysaccharide nanogels - a versatile delivery system to augment the utility of bioactive cargo.” Nanomedicine pii: S1549-9634(18)30545-8 doi: 10.1016/j.nano.2018.10.008.
- Alumasa JN, Goralski TDP, Keiler KC (2017) “Tetrazole-Based trans-Translation Inhibitors Kill Bacillus anthracis Spores to Protect Host Cells.” Antimicrobial Agents & Chemotherapy 61:e01199-17.
- Alumasa JN, Manzanillo PS, Peterson ND, Lundrigan T, Baughn AD, Cox JS, Keiler KC (2017) “Ribosome Rescue Inhibitors Kill Actively Growing and Nonreplicating Persister Mycobacterium tuberculosis Cells.” ACS Infectious Diseases 3:634-644.
- Dillon NA, Peterson ND, Feaga HA, Keiler KC, Baughn AD (2017) “Anti- tubercular Activity of Pyrazinamide is Independent of trans-Translation and RpsA.” Scientific Reports 7:6135.
- Keiler KC, Jackson KL, Jaworski L, Lopatto D, Ades SE (2017) “Teaching broader impacts of science with undergraduate research.” PLoS Biology 15: e2001218.
- Feaga HA, Quickel MD, Hankey-Giblin PA, Keiler KC (2016) “Human cells require non-stop ribosome rescue activity in mitochondria.” PLoS Genetics 12: e1005964.