Within the College of Veterinary Medicine and Biomedical Sciences and the Department of Microbiology, Immunology and Pathology, the MRL is presently made up of the laboratories of 20 principal investigators.

Faculty serve as major advisors for 49 undergraduate students enrolled in the Microbiology program of study, 17 post-doctoral fellows, 13 Ph.D. students, 2 veterinary residents pursuing M.S./Ph.D. degrees and specialty board certification, and 2 thesis-based M.S. degree students enrolled in several interdisciplinary programs. The MRL is also home to numerous visiting scientists from all over the world.

With a research team comprised of a total of 168 research personnel, including Faculty, Students, Post-Doctoral Fellows, Research Scientists, Visiting Scientists, Research Associates and Research Coordinators, the MRL is one of the pillars of the Infectious Disease program of DMIP. This program, which was named the first Supercluster at CSU, was designed to speed the transition of life saving research on infectious diseases from the academic world to the global market place.

History of the MRL

Dr. Patrick Brennan joins the Department of Microbiology

The present day MRL had its genesis in the recruitment of Dr. Patrick Brennan to the Department of Microbiology in August 1980.

Dr. Brennan first conducted research on Mycobacterium tuberculosis/tuberculosis as a PhD graduate student under Professor Frank A. Winder at Trinity College, Dublin in the early 1960s, and continued in that direction as a Post-Doctoral Fellow under Professor Clint Ballou at the University of California, Berkeley, and, subsequently on his return to Dublin as a faculty member at Trinity College, Dublin and University College, Dublin. In 1975 he followed his wife, Dr. Carol Blair, back to the US, she to CSU and he to National Jewish Hospital, Denver.

In 1980 he was appointed Associate Professor in the Department of Microbiology.  He brought with him a very successful program, and associated grant from NIH, NIAID (a grant which subsequently was to continue until 2009 including two 10-year MERIT Awards), on the molecular basis of antigenic heterogeneity in the Mycobacterium avium complex and the cell wall of M. tuberculosis.

In addition while he was at National Jewish Hospital, Denver, he had been awarded a contract from NIAID for the isolation of Mycobacterium leprae from infected armadillo tissues and definition of its antigenic

repertoire (this Contract was to be continually renewed over the subsequent 30 years and is still in existence). Based on this funding Dr. Brennan recruited Drs. Shirley Hunter, Delphi Chatterjee and Michael McNeil and, in more recent times, Drs. Dean Crick, Varalakshmi Vissa, John Spencer, and Mary Jackson (the five are now Professors in the Department and subsequently developed their own programs and grants in the context of the MRL). Some of the graduate students who arose from these programs and are now also the faculty backbone of the Department, the MRL and the IDRC (Infectious Disease Research Center), are Drs. John Belisle, Richard Slayden, and Karen Dobos.

Dr. Ian Orme brings a focus on immunology and use of animal models

The recruitment of Dr. Ian Orme to a tenured faculty slot in the Department in 1986 led to the introduction of research to CSU on the immunology of tuberculosis and the use of animal models of the disease and the formal founding of the Mycobacteria Research Laboratories (MRL).

Dr. Orme had impeccable pedigree on TB research having come from University College, London via the famed Trudeau Research Institute in Saranac Lake, New York, where he had worked with the likes of Drs. Frank Collins, George Mackaness and Robert North on animal models of TB. Dr. Orme was a bona fide immunologist and had done pioneering work on the cellular basis of protective immunity in TB and he had his own NIH funding. He brought with him a very able Research Associate, Alan Roberts, and was subsequently able to recruit Postdoctoral Fellows and Research Scientists such as Drs. Andrea Cooper and Joanne Turner who now lead major TB research programs at Trudeau and Ohio State University, respectively, Drs. Anne Lenaerts, Angelo Izzo and Mercedes Gonzalez-Juarrero, now Faculty members in the Department and MRL with their own programs.

Among the graduate students from Dr. Orme’s programs who have gone on to very successful research careers are Drs. Katherine Bosio and Susan Baldwin, and Dr. Diane Ordway, now an Assistant Professor within the Department with her own research program.

Growing faculty increases depth and breadth of research

Dr. John Belisle, originally a graduate student of Dr. Brennan, returned to the MRL and the Department in 1995 after serving as a post-doctoral fellow at the University of Texas Southwestern Medical Center.  He is now a Professor in the department, a recipient of the Monfort Professor award, and the director of a Program of Research & Scholarly Excellence, the Infectious Disease Research and Response Network (IDR2N).

Dr. Mary Jackson, originally a Post-Doctoral Fellow with Dr. Brennan, was recruited to the MRL and the Department in 2007 from the famed Pasteur Institute, Paris, as a mycobacterial geneticist; she is now an Associate Professor.

Dr. Randall Basaraba was originally a veterinarian pathologist in the Diagnostic Laboratory within the College, but joined Dr. Orme’s program as an anatomical pathologist specializing in the pathology of TB; he now also has his own research program.

NIH, NIAID-sponsored contracts

NIH, NIAID-sponsored Contracts have been the life blood of the MRL, initially the Leprosy Contract (Brennan, PI), then the TB Contract (initially Brennan as PI, followed by Belisle and Dobos), Animal TB Models for vaccine development and testing (Orme/Izzo), for drug evaluations (Orme/Lenaerts). First integration of MRL in the form of some of these contracts, specifically bulk culture of Mycobacterium tuberculosis, into what is now IDRC took place in 1995 with the establishment of a BSL-3 suite within the AIDL (Arthropod-borne and Infectious Diseases Laboratory) complex. Subsequently, this was moved in conjunction with the animal models to the new RBL (Regional Biocontainment Laboratory) in 1997. Current programs include mycobacterial drug screening programs under the leadership of Dr. Anne Lenaerts and in vivo vaccine efficacy programs under the direction of Dr. Angelo Izzo.

In addition, CSU continues to generate specialized mycobacterial biological reagents under the leadership of Dr. Karen Dobos; all materials are now available at no cost through the Biodefense and Emerging Infections Research Resources Repository (BEI Resources). In recent times, grants from the Bill and Melinda Gates Foundation have added considerably to the research funding and prestige of the Laboratories.

Dr. Brennan and Dr. Orme formally founded the MRL in 1986. Dr. Brennan was the first Director, followed some years later by Dr. Orme, then Dr. Belisle, Dr. Crick and currently Dr. Jackson. The Unit has drawn up a formal charter, holds one all-MRL Biannual Meeting, a Seminar Series every other week with internal and invited speakers, and holds an annual picnic and several social events during the year.

MRL CLASSICS 1967-1996

Brennan, P., and C.E. Ballou.  Biosynthesis of mannophosphoinositides by Mycobacterium phlei — a family of dimannophosphoinositides.  J. Biol. Chem. 242: 3046-3056, 1967.

Brennan, P.J., and M.B. Goren.  Structural studies on the type-specific antigens and lipids of theMycobacterium avium–Mycobacterium intracellulare-Mycobacterium scrofulaceum serocomplex.  J. Biol. Chem. 254: 4205-4211, 1979.

Brennan, P.J., G.O. Aspinall, and J.E. Nam Shin.  Structure of the specific oligosaccharides from the glycopeptidolipid antigens of serovars in the Mycobacterium avium–Mycobacterium intracellulare–Mycobacterium scrofulaceum complex.  J. Biol. Chem. 256: 6817-6822, 1981

Hunter, S.W., T. Fujiwara, and P.J. Brennan.  Structure and antigenicity of the major specific glycolipid antigen of Mycobacterium leprae.  J. Biol. Chem. 257: 15072-15078, 1982

Hunter, S.W., R.C. Murphy, K. Clay, M.B. Goren, and P.J. Brennan.  Trehalose-containing lipooligosaccharides. J. Biol. Chem. 258: 10481- 10487, 1983

McNeil, M., D. Chatterjee, S.W. Hunter, and P.J. Brennan.  Mycobacterial glycolipids: isolation, structures, antigenicity, and synthesis of neoantigens, In Methods in Enzymology (V. Ginsburg, ed.) Academic Press,
San Diego, 179: 215-242, 1989.

Fujiwara, T., S.W. Hunter, S.N. Cho, G.O. Aspinall, and P.J. Brennan.  Chemical synthesis and serology of disaccharides and trisaccharides of phenolic glycolipid antigens from the leprosy bacillus and preparation of a disaccharide protein conjugate for serodiagnosis of leprosy.  Infect. Immun. 43: 245-252, 1984.

Hunter, S.W., T. Fujiwara, R.C. Murphy, and P.J. Brennan.  N-Acylkansosamine: a novel N-acylaminosugar from the trehalose- containing lipooligosaccharide of antigens of Mycobacterium kansasii.  J. Biol. Chem.259:
9729-9734, 1984.

Hunter, S.W., H. Gaylord, and P.J. Brennan.  Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli.  J. Biol. Chem. 261: 12345-12351, 1986.
Daffe, M., P.J. Brennan, and M. McNeil.  Predominant structural features of the cell wall arabinogalactan ofMycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by 1H and 13C NMR analyses.  J. Biol. Chem. 265: 6734-6743, 1990.

Hunter, S.W., and P.J. Brennan.  Evidence for the presence of a phosphatidylinositol anchor on the lipoarabinomannan and lipomannan of Mycobacterium tuberculosis.  J. Biol. Chem. 265: 9272-9279, 1990

McNeil, M., M. Daffe, and P.J. Brennan.  Evidence for the nature of the link between the arabinogalactan and peptidoglycan components of mycobacterial cell walls.  J. Biol. Chem. 265: 18200-18206, 1990.

McNeil, M., M. Daffe, and P.J. Brennan.  Location of the mycolyl ester substituent in the cell walls of mycobacteria.  J. Biol. Chem. 266: 13217-13223, 1991

Chatterjee, D., S.W. Hunter, M. McNeil, and P.J. Brennan.  Lipoarabinomannan: multiglycosylated form of the mycobacterial mannosylphosphatidylinositols. J. Biol. Chem. 267: 6228-6233, 1992.

Chatterjee, D., K. Lowell, B. Rivoire, M. McNeil, and P.J. Brennan.  Lipoarabinomannan of Mycobacterium tuberculosis:  capping with mannosyl residue in some strains.  J. Biol. Chem. 267: 6234-6239, 1992.

Wolucka, B.A., M.R. McNeil, E. de Hoffmann, T. Chojnacki, and P.J. Brennan.  Recognition of the lipid intermediate for arabinogalactan/arabinomannan biosynthesis and its relation to the mode of action of
ethambutol on mycobacteria.  J. Biol. Chem. 269: 23328-23335, 1994.

Mikušová, K., M. Mikuš, G.S. Besra, I. Hancock, and P.J. Brennan. Biosynthesis of the linkage region of the mycobacterial cell wall.  J. Biol. Chem. 271: 7820-7828, 1996.