John R. Kirby, PhD - Professor of Microbiology, University of Iowa, IA, USA
Interview and Presentation from Dr. John Kirby
Topic : "Xenobiotic Disruption of the Microbiome and Metabolic Consequences"
Feb 9th, 2.30 PM EST, 1.30 PM CST, 11.30AM PST, 7.30 PM GMT, 1.00 AM IST Feb 10th 2016
John R Kirby, PhD
Professor, Departments of Microbiology and Urology
Director, Residents Research in Urology
Chair, Graduate Admissions in Microbiology
Program Director, Sloan Center for Exemplary Mentoring
Member, Interdisciplinary Programs in Informatics and Genetics
Fraternal Order of Eagles’ Diabetes Research Center
A. Personal Statement
Our major areas of investigation focus on microbial communities. Over the last two decades, I have been investigating signal transduction in relatively diverse bacteria ranging from soil dwelling spore formers (Bacillus subtilis and Myxococcus xanthus) to biofilm forming pathogens (Haemophilus influenzae, Neisseria gonorrhoeae, & Staphylococcus aureus). Work in my laboratory has expanded the understanding of chemosensory systems and closely related two-component signal transduction systems (TCS) and demonstrated their versatility for regulation of motility and gene expression. We identified the first example of a chemosensory system that regulates gene expression to affect biofilm formation and sporulation and we were the first laboratory to demonstrate a biochemical interaction between a chemosensory system and a prototypical two-component system. We coined the term “predataxis” to describe the ecology of a biofilm destroyer, M.xanthus, which utilizes a chemosensory system to regulate its predation upon other species of bacteria. More recently, we have extended our investigation of microbial communities to the gut microbiome. In particular, we are interested in the effect of xenobiotics for their capacity to disrupt the microbial communities with deleterious consequences on metabolism, in both mice and humans.
B. Positions and Honors
Academic Positions
2002-2006 Assistant Professor School of Biology, Georgia Institute of Technology
2007-2014 Associate Professor Department of Microbiology, University of Iowa
2014-present Professor Department of Microbiology, University of Iowa
2007-present Faculty Center for Biocatalysis and Bioengineering
2007-present Faculty Medical Scientist Training Program
2009-present Faculty Interdisciplinary Graduate Program in Genetics
2013-present Faculty Interdisciplinary Graduate Program in Informatics
2013-present Faculty Fraternal Order of Eagles Diabetes Research Center
2014-present Faculty Sloan Center for Exemplary Mentoring
2014-present Faculty Interdisciplinary Institute for Human Genetics
2014-present Faculty Behavioral-Biomedical Interface Training Program
2015-present Faculty Department of Urology, University of Iowa
2015-present Director, Resident Research Department of Urology, University of Iowa
Professional positions
2006-2007 Division Chair American Society for Microbiology: Cell & Structural Biology
2007-2008 Division Advisor American Society for Microbiology: Cell & Structural Biology
2006-2010 Instructor Cold Spring Harbor Laboratory: Advanced Bacterial Genetics
2012-present Science Advisor Hennepin Life Sciences
2013-present Academic Editor PLOS ONE
2014-present Editorial Advisory Board Molecular Microbiology
2015-present Editorial Advisory Board Frontiers in Microbiology
2016 Chair GRC: Sensory Transduction in Microorganisms
Reviewer: National Science Foundation: Signal Transduction (2011), Systems Biology (2013, 2014) and multiple journals: Applied & Environmental Microbiology, Archives of Microbiology, Bacteriophage, Biofilms, Bioorganic & Medicinal Chemistry, Biophysical Journal, BMC Genomics, BMC Evolutionary Biology, Current Microbiology, Diabetes, Environmental Microbiology, F1000 Biology, FEMS Microbial Letters, FEMS Microbial Ecology, Genetics, Genome Biology, Journal of Bacteriology, Journal of Molecular Biology, Journal of the Royal Society Interface, Journal of Visualized Experiments, mBio, Microbiology, Medical Microbiology & Immunology, Molecular Microbiology, Molecular Phylogenetics & Evolution, Nature, Nature Chemical Biology, Nature Communications, Nature Scientific Reports, Nucleic Acids Research, PNAS, PLoS Computational Biology, PLoS Genetics, PLoS ONE, Nucleic Acids Research, Synthetic Biology, Trends in Microbiology
Honors
1992-1998 Outstanding Teaching Awards, Chemistry, UIUC (4 times)
2004 Dean Griffin "Go the Extra Mile Award", Georgia Tech
2008 New York Times, Science Times, research highlight
2009 Popular Science, research highlight
2009 Welt der Wunder, Germany, research highlight
2009 Sciences et Avenir, France, research highlight
2009 Muy Interesante, Spain, research highlight
2009 McGraw-Hill, Willey: Prescott’s Microbiology, 8th edition, research included in text
2010 FEMS Microbiology Reviews, Cover 2010
2010 W.W.Norton, Microbiology 2nd edition by Slonczewski and Foster, research highlighted in text
2010 Centre for Intelligent Machines, McGill University, research highlight
2012 This Week in Microbiology “A Mecca for Microbiology”
2013 Microbial Diversity, ASM Press, research highlight
2013 Small Things Considered, research highlight
2013 New York Times, Science Times, research highlight
2014 MicrobeWiki, research highlight
2014 Nature Reviews Microbiology, research highlight
2014 Spotlight, Applied & Environmental Microbiology
2014 American Society for Microbiology: Divisional Group IV Representative, Nominee
2015 Jones & Bartlett Learning, Fundamentals of Microbiology, 3rd edition, research highlight
2015 Spotlight, Applied & Environmental Microbiology
2015 Principles of Microbial Diversity, ASM Press, research highlight
2015 Microbe World PodCast-BacterioFiles “Myxococcus Menace Motivates Megastructures”
2015 Small Things Considered, Megastructures: Defense Fortifications of Bacillus subtilis for Protection from Myxococcus xanthus
2015 Iowa Microbiology Microbiome Initiative (Director)
2015 ProPhage Blog "Study Sheds New Light on the Roles of Viruses in Weight Gain"
2015 Ars Technica: "Psychiatric drug – not antibiotic – messes with gut microbes, spur obesity"
2015 BioTechniques, TechNews: "The Bacteria Among Us"
2015 IowaNow: "Gut microbes: Burning calories while you sleep?"
C. Contribution to Science
Work in my laboratory has expanded the understanding of chemosensory systems and closely related two-component signal transduction systems (TCS) and demonstrated their versatility for regulation of motility and gene expression. In collaboration with Adam Arkin and Chris Rao, we generated a mathematical model for control of chemotaxis in E. coli and Bacillus subtilis.
- Rao, CV, Kirby, JR, and Arkin, AP. (2004) Design and Diversity in Bacterial Chemotaxis: A Comparative Study of Escherichia coli and Bacillus subtilis. PLoS Biology 2: 239-252. PMID: 14966542.
- Rao, C. V., J. R. Kirby and A. P. Arkin. (2005) Phosphatase Localization in Bacterial Chemotaxis: Divergent Mechanisms, Convergent Principles. Phys. Biol. 2:148-158.
- Kirby, JR. (2009) Chemotaxis-like Regulatory Systems: Unique Roles in Diverse Bacteria. Annual Reviews of Microbiology. 63: 45-59. PMID: 19379070
- Moine, A, Agrebi, R, Espinosa, L, Kirby, JR, Zusman DR, Mignot, T, and Mauriello, EMF. (2014) Functional Organization of a Multimodular Bacterial Chemosensory Apparatus. PLoS Genetics 10(3):e1004164.
We identified the first example of a chemosensory system that regulates gene expression to affect biofilm formation and sporulation which were previously thought to exclusively control motility (i.e. chemotaxis). Furthermore, we were the first laboratory to demonstrate a biochemical interaction between a chemosensory system and a prototypical two-component system. We also clarified the role for specific residues for dual-function kinases and phosphatases.
- Willett, JW and Kirby, JR. (2011) CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in Myxococcus xanthus. mBio 2(4): e00110-11.
- Willett, JW and Kirby, JR. (2012) Genetic and Biochemical Dissection of a HisKA Domain Identifies Residues Exclusively Required for Kinase and Phosphatase Activities. PLoS Genetics 8(11): e1003084.
- Willett, JW, Tiwari, N, Müller, S, Hummels, KR, Houtman, J, Fuentes, EJ and Kirby JR. (2013) Specificity Residues Determine Binding Affinity for Two-Component Signal Transduction Systems. mBio 4(6):e00420-13.
- Darnell, CL, Wilson, JM, Tiwari, N, Fuentes, EJ and Kirby JR. (2014) “Chemosensory regulation of a HEAT-repeat protein couples aggregation and sporulation in Myxococcus xanthus”. J Bacteriol. 196(17):3160-8. doi: 10.1128/JB.01866-14.
We coined the term “predataxis” to describe the ecology of a biofilm destroyer, M.xanthus, which utilizes a chemosensory system to regulate its predation upon other species of bacteria.
- Berleman, JE, Chumley, T, Cheung, P, and Kirby, JR. 2006 Rippling is a predatory behavior in Myxococcus xanthus. J. Bacteriol. 188: 5888-95.
- Berleman, JE and Kirby, JR. (2007) Multicellular development in Myxococcus xanthus is stimulated by predator-prey interactions. J. Bacteriol. 189: 5675-82. PMID: 17513469
- Berleman, JE, Scott, JC, Chumley, T, and Kirby, JR. (2008) Predataxis behavior in Myxococcus xanthus. Proc. Natl. Acad. Sci. USA. 105: 17127-17132. PMID: 18952843
- Berleman, JE and Kirby, JR. (2009) Deciphering the hunting strategy of a bacterial wolfpack. FEMS Microbiology Reviews. 33: 942-957. PMID: 19519767
We have established a predator-prey competition system to elucidate the role for secondary metabolites in the regulation of complex multicellular communities.
- Müller, S, Willett, JW, Bahr, SM, Darnell, CL, Hummels, KR, Dong, CK, Vlamakis, HC, and Kirby, JR. (2013) Draft Genome Sequence of Myxococcus xanthus Wild-Type Strain DZ2, a Model Organism for Predation and Development. Genome Announcements 1(3):e00217-13. doi:10.1128/genomeA.00217-13.
- Müller, S, Strack, SN, Hoefler, BC, Straight, P, Kearns DB and Kirby, JR. (2014) “Bacillaene and sporulation protects Bacillus subtilis from predation by Myxococcus xanthus”. Appl. Environ. Microbiol. 80(18):5603-10.
- Müller, S, Strack, SN, Ryan SE, Kearns DB and Kirby, JR. (2015) “Predation by Myxococcus xanthus Induces Bacillus subtilis to Form Spore-Filled Megastructures” Appl. Environ. Microbiol. 81(1):203-10.
We have established gut microbiome research in our lab and are interested in the effect of xenobiotics for their capacity to disrupt the microbial communities with deleterious consequences on metabolism, in both mice and humans.
- Bahr, SM, Tyler, B.C., Wooldridge, N., Butcher, B.D., Burns, T.L., Teesch, L.M., Oltman, C.L., Azcarate-Peril, M.A., Kirby, J.R.*, Calarge, C.A. “Use of the Second Generation Antipsychotic, Risperidone, and Secondary-Weight gain are Associated with an Altered Gut Microbiota in Children.” Translational Psychiatry (Nature) 5, e652; doi:10.1038/tp.2015.135.
- Bahr, SM, Weidemann, BJ, Castro, AN, Walsh, JW, deLeon O, Burnett, CML, Pearson, NA, Murry, DJ, Grobe, JL, Kirby, JR. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure. EBioMedicine doi:10.1016/j.ebiom.2015.10.018
D. Research Support
Ongoing Research Support
NIH R01 $4,187,832 4/1/2014-3/31/2019
Lysine Acetylation in N. gonorrhoeae Quorum Sensing and Biofilm Formation
PI: Kirby JR and Gibson, B.
The goal of this study is to characterize the role of acetylation of cytosolic proteins affecting biofilm formation in Neisseria gonorrhoeae with a primary focus on the MisSR two component signal transduction system.
NSF MCB-1244021 $938,034 2/1/2013-1/31/2017
Two Component Signal Transduction Networks in Myxococcus xanthus
PI: Kirby
The goal of the this study is to identify the two component histidine kinase signaling networks controlling development in bacteria and generate a mathematical model to describe those networks.
Fraternal Order of Eagles Diabetes Research $100,000 9/1/2014-8/31/2016
Non-Aerobic Resting Metabolism: An Untapped Obesity Target?
Investigators: Grobe (PI) and Kirby
The goal of this study is to identify the role of xenobiotic disruption of the microbiota and its metabolic consquences.
Stinski Innovator Award, University of Iowa $230,000 10/1/2014-9/30/2016
Xenobiotics Disruption of the Microbiome and Metabolic Consequences
PI: Kirby JR
Kate Stillman (Donation via Terry Wahls Foundation) $134,000 7/1/2015-6/30/2016
Diet Manipulation of the Microbiome During Multiple Sclerosis
PI: Kirby JR
Recently Completed Research Support
University of Iowa – Carver Trust Collaborative Pilot Grant $100,000 1/1/2013-12/31/2014
Role of CD40 in Type 2 Diabetes, Obesity and the Gut Microbiome
Investigators: Bishop (PI) and Kirby
The goal of this study is to identify the role of CD40 affecting weight gain, diabetes and the microbiome in the mouse model.
Fraternal Order of Eagles Diabetes Research $100,000 9/1/2012-8/31/2014
Peripheral Mechanism of Antipsychotic-Induced Weight Gain and Insulin Resistance: a Gut Microbiome Study.
Investigators: Calarge (PI) and Kirby
The goal of this study is to identify the role of the microbiome during weight gain associated with treatment by Risperidone in human subjects.
Pending Research Support
Title: Predator-Prey Dynamics are Regulated by Intercellular Signaling in Soil Bacteria
Source: NSF
Total Funds: $2,380,134
Funding period: 2/1/2016-2/1/2020
Investigators: Kirby JR (PI), Kearns, DB, Straight, PD, Xavier, J
Title: Role of Inflammation, Obesity & Microbiome in Urological Disorders
Source: NIH U54: George M. O’Brien Urology Cooperative Research Centers Program
Direct Funds: $5,000,000
Funding period: 12/1/2015-11/30/2020
Investigators: Kreder (PI) et al
Title: Role of the Gut Microbiota in Manifestation and Diet-dependent Rescue of Genetically Inherited Behavioral Abnormalities
Source: NIH R21
Direct Funds: $500,000
Funding period: 4/1/2016-3/31/2018
Investigators: Kitamoto T (PI), Kirby JK
Title: Functional Rehabilitation of Type 2 Diabetic Peripheral Neuropathy with Nicotinamide Riboside
Source: Veterens Administration, Rehabilitation Research & Development
Direct Funds: $1,100,000
Funding period: 11/1/2015 – 10/31/2019
Investigators: Charles Brenner (PI), Randy Kardon, Mark Yorek, Kirby JR
