Dr Apoorva Bhatt PhD

Senior Lecturer in Molecular Microbiology
Program Leader- MSc Microbiology and Infection

School of Biosciences

bhatt-apoorva

Contact details

Telephone +44 (0)121 41 45893

Fax +44 (0)121 41 45925

Email a.bhatt@bham.ac.uk

School of Biosciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

About

Apoorva Bhatt - Research in 60 seconds videoDr. Bhatt is a Lecturer in Molecular Microbiology in the School of Biosciences. A prestigious Fellowship- a Career Development Award from the Medical Research Council-enabled him to set up his research group at the University of Birmingham in 2006. Dr.Bhatt’s research interests include studying pathogenic mycobacteria and how they cause disease, with a particular focus on Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). This includes using a genetic approach to identify pathways involved in the biosynthesis of virulence-related metabolites.

Qualifications

  • PhD (Bacterial Genetics)
  • BSc and MSc (Microbiology)

Biography

2011-Present: Lecturer in Molecular Microbiology

2006-2011: Medical Research Council Fellow (Career Development Award)

2002-2006: Research Associate, Howard Hughes Medical Institute, Albert Einstein College of Medicine

2000-2002: Research Associate, University of Cambridge

1996-2000: PhD, John Innes Centre, Norwich

Teaching

  1. Undergradaute Lectures: BIO305 and BIO317
  2. Undergraduate Practicals: BIO151, BIO262, BIO305
  3. MSc Lectures: BIOM08, BIOM22
  4. MSc Practicals: BIOM22
  5. ERASMUS teaching exchange with the Université Joseph Fourier, Grenoble, France.
  6. Final year undergraduate, MRes and MSc research projects

Postgraduate supervision

PhD studentships are awarded each year competitively within the School of Biosciences. Funding options are also available for international students including a studentship from the Darwin Trust of Edinburgh.

For a list of possible PhD projects offered by Dr Bhatt www.findaphd.com/search/customlink.asp?inst=birm-Biol&supersurname=Bhatt

Research

Research Theme within School of Biosciences: Molecular Microbiology

Lipid Metabolites of mycobacteria: pathways to biosynthesis and role in virulence

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis remains the most successful human pathogen. Though considered to be under control only 20 years ago, a number of factors like the spread of HIV and the emergence of drug resistant MTB strains have led to the resurgence of this disease. There is thus a clear and urgent need to extend our understanding of the physiology and pathogenicity of MTB with the aim of developing new therapeutics and vaccines.

Complex lipids play an important role in the biology of the bacterium as a large proportion of the genome contains genes proposed to be involved in lipid biosynthesis. A distinct lipid rich outer envelope helps MTB counteract a number of inhospitable conditions in vivo, and many mycobacterial lipids display immunomodulatory activities when tested in models of infection. Mycobacterial lipids thus play an important role in virulence. Furthermore, some of these lipids have been shown to be essential for growth and the enzymes involved in the biosynthesis of these lipids represent potential drug targets. The pathways involved in lipid biosynthesis thus merit a detailed study.

A broad aim of my research is understand how mycobacterial lipids are made, and the impact they have on virulence. We use a genetic approach to address these questions by generating mutant strains that are defective in these pathways. Research in my laboratory is funded by a Career Development Award, and Research Grants from the Medical Research Council.

Publications

(1)     Ly D., Kasmar A.G., Cheng T.Y., de Jong A., Huang S., Roy S., Bhatt A., van Summeren R.P., Altman J.D., Jacobs W.R. Jr, Adams E.J., Minnaard A.J., Porcelli S.A. and Moody D.B. (2013) CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. J Exp Med 2013 210:729-741.

(2)     Varela C., Rittmann D., Singh A., Krumbach K., Bhatt K., Eggeling L., Besra G.S. and Bhatt A. (2012) MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria. Chem Biol 19:498-506.

(3)     Yamada H., Bhatt A., Danev R., Fujiwara N., Maeda S., Mitarai S., Chikamatsu K., Aono A., Nitta K., Jacobs WR Jr. and Nagayama K. (2012) Non-acid-fastness in Mycobacterium tuberculosis ΔkasB mutant correlates with the cell envelope electron density. Tuberculosis 92:351-357.

(4)     Sarkar D., Sidhu M., Singh A., Chen J., Lammas D.A., van der Sar A.M., Besra G.S. and Bhatt A. (2011) Identification of a glycosyltransferase from Mycobacterium marinum involved in the addition of a caryophyllose moiety in lipooligosaccharides. J Bacteriol 193:2336-2340.

(5)    Alderwick L.J., Lloyd G.S., Ghadbane H., May J.W., Bhatt A., Eggeling L., Fütterer K., and Besra G.S. (2011) The C-terminal domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC is a lectin-like carbohydrate binding module. PLoS Pathog 7(2):e1001299.

(6)     Khan S., Nagarajan N.S., Parikh A., Samantaray S., Singh A., Kumar D., Roy R.P., Bhatt A. and Nandicoori V.K. (2010) Phosphorylation of enoyl-ACP reductase InhA impacts mycobacterial growth and survival. J Biol Chem 285: 37860-37871.

(7)     Taylor R.C., Brown A.K., Singh A., Bhatt A. and Besra G.S. (2010) Characterization of a beta-hydroxybutyryl-CoA dehydrogenase from Mycobacterium tuberculosis. Microbiol 156: 1975-1982.

(8)     Birch H.L., Alderwick L.J., Appelmelk B.J., Maaskant J., Bhatt A., Singh A., Nigou J., Eggeling L., Geurtsen J. and Besra G.S. (2010) A truncated lipoglycan from mycobacteria with altered immunological properties. Proc Natl Acad Sci 107: 2634-2639.

(9)     Chen J., Kriakov J., Singh A., Jacobs Jr. W.R., Besra G.S. and Bhatt A. (2009)  Defects in glycopeptidolipid biosynthesis confer phage I3 resistance in Mycobacterium smegmatis  Microbiol 155: 4050-4057.

(10)   Brown A.K., Taylor R.C., Bhatt A., Fütterer K. and Besra G.S. (2009)  Platensimycin activity against mycobacterial b-ketoacyl-ACP synthases.  PLoS ONE 17: e6306.

(11)   Bhatt A., Brown A.K., Singh A., Minnkin D.E. and Besra G.S. (2008)  Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing b-oxo-mycolic acid analogs and accumulation of ketones.  Chem Biol 15: 930-939.

(12)   Bhatt A. and Jacobs Jr. W.R. (2008) Testing gene essentiality in mycobacteria using specialized transduction and inducible promoters. Mycobacteria Protocols, 2nd Ed, Humana Press. Ed. Tanya Parish and Amanda Brown.

(13)   Bhowruth V., Alderwick L.J., Brown A.K., Bhatt A. and Besra G.S. (2008)  Tuberculosis: a balanced diet of lipids and carbohydrates.  Biochem Soc Trans 36: 555–565.

(14) Birch H.L., Alderwick L.J., Bhatt A., Rittman D., Krumbach K., Singh A., Yu B., Lowary T.L., Eggeling L. and Besra G.S. (2008)  Biosynthesis of mycobacterial arabinogalactan: identification of a novel (1→3) arabinofuranosyltransferase.  Mol Microbiol 65: 1191-1206.

(15) Mishra A.K., Alderwick L.J., Rittman D., Wang C., Bhatt A., Jacobs Jr. W.R., Takayama K., Eggeling L. and Besra G.S. (2008)  Identification of a novel a(1→6) mannopyranosyltransferase MptB from Corynebacterium glutamicum by deletion of a conserved gene, NCgl1505 affords a lipomannan- and lipoarabinomannan-deficient mutant.  Mol Microbiol 68: 1595-1613.

(16) Dover L.G., Bhatt A., Bhowruth V., Willcox B.E. and Besra G.S. (2008)  New drugs and vaccines for drug-resistant Mycobacterium tuberculosis infections.  Expert Rev Vaccines 7: 481-497

(17)   Bhatt A./Brown A.K., Singh A., Saparia E., Evans A.F. and Besra G.S. (2007)  Identification of the dehydratase component of the mycobacterial mycolic acid synthesizing fatty acid synthase-II complex.  Microbiol 153: 4166-4173.[ Equal authorship].

(18)   Brown A.K., Papaemmanouil A., Bhowruth V., Bhatt A., Dover L.G. and Besra G.S. (2007)  Flavonoid inhibitors as novel antimycobacterial agents targeting Rv0636, a putative dehydratase enzyme involved in Mycobacterium tuberculosis fatty acid synthase II.  Microbiol 153: 3314-3322.

(19)   Bhatt A., Molle V., Besra G.S., Jacobs Jr. W.R. and Kremer L. (2007)  The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic acid biosynthesis, acid fastness, pathogenesis and in drug development.  Mol Microbiol 64: 1442-1454.

(20)   Bhatt A., Fujiwara N., Bhatt K., Gurcha S.S., Kremer L., Chen B., Chan J., Porcelli S., Kobayashi K., Besra G.S. and Jacobs Jr. W.R. (2007)  Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice.  Proc Natl Acad Sci (USA) 104: 5157-5162.

(21)   Bhatt K., Gurcha S.S., Bhatt A., Besra G.S. and Jacobs Jr. W.R. (2007)  Two polyketide-synthase-associated acyltransferases are required for sulfolipid biosynthesis in Mycobacterium tuberculosis. Microbiol 153: 513-520.

(22)   Ojha A., Anand M., Bhatt A., Kremer L., Jacobs Jr. W.R. and Hatfull G.F.  (2005)  GroEL1: A dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria.  Cell  123: 861-873.

(23)   Bhatt A., Kremer L., Dai A.Z., Sacchettini J.C. and Jacobs Jr. W.R.  (2005)  Conditional depletion of KasA, a key enzyme of mycolic acid biosynthesis, leads to mycobacterial cell lysis.  J Bacteriol  187: 7596-7606.

(24)    Bhatt A., Stark C.B.W., Harvey B.M., Gallimore A.R., Spencer J.B., Staunton J. and Leadlay P.F. (2005)  Accumulation of an E,E,E,-Triene by a polyether-producing polyketide synthase when oxidative cyclization is wholly blocked.  Angew Chem  44: 7075-7078.

(25)    Matsunaga I., Bhatt A., Young D.C., Cheng T-Y., Besra G.S., Briken V., Porcelli S.A., Jacobs Jr. W.R. and Moody D.B. (2004)  Mycobacterium tuberculosis pks12 produces a novel polyketide presented by CD1c to T Cells. J Exp Med 200: 1559-1569.

(26)    Bhatt A. and Jacobs Jr. W.R. (2003)  Conjugal rites of mycobacteria. Nat Genet 34: 3-4.

(27)    Olinyk M., Stark C.B.W., Bhatt A., Jones M.A., Hughes-Thomas Z.A., Wilkinson C., Olinyk Z., Demydchuk Y., Staunton J. and Leadlay P.F. (2003)  Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Mol Microbiol  49:1179-1190.

(28)    Bhatt A., Melton R.E., Kieser H.M. and Kieser T. (2002)  Plasmid transfer from Streptomyces to Mycobacterium smegmatis by spontaneous transformation. Mol Microbiol 43: 135-146.

(29)    Bhatt A., Stewart G. and Kieser T. (2002)  Transposition of Tn4556 of Streptomyces fradiae in Mycobacterium smegmatisFEMS Microbiol Lett 206: 241-246.

(30)    Bhatt A. and Kieser T. (1999)  Transposition of IS117 of Streptomyces coelicolor A3(2) in Mycobacterium smegmatisMicrobiol 145: 1201-1207.

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