IFCPAR AR (ENGLISH) for CD - CEFIPRA

10
Life and Health Sciences
Dr. R.S. Gokhale
National Institute of Immunology
New Delhi
Dr. Jean-Marc Reyrat (late)
Faculté de Médecine necker-Enfants
Malade de Pathogénie des Infections,
Systémiques, INSERM UMR570
Faculté de Médicine,
Paris
Project 3403-3
ANALYSIS OF GPLs BIOSYNTHESIS IN MYCOBACTERIA
IFCPAR
Indo-French Centre for the Promotion of Advanced Research
Duration: Three years and six months (November, 2006 to
April, 2010)
Objectives
The collaborators proposed to undertake a systematic gene
knock out strategy in order to unravel the biosynthetic steps and
the mechanisms of transport and localisation of the GPLs, a
small peptidoglycolipid, produced by a range of various
mycobacterial species.
Mutants of M.smegmatis were to be constructed in the
laboratory of French Collaborator using the standard
molecular genetic methods and GPLs derivatives were to be
structurally characterized in the laboratory of Indian
Collaborator. The function of proteins were to be
unambiguously characterized by the isolation of protein with
demonstrable activities. This collaboration allowed a precise
molecular understanding of the biosynthetic pathway and the
mechanism of transport of GPLs molecules and shed light on
the metabolism of small molecules in mycobacteria.
Moreover, a number of other mycobacterial GPLs producing
species are currently under sequence. Comparative genomics
between this various species should enable the
characterisation of the genomic region responsible for the
subtle biochemical modifications of the GPLs core.
Accomplishments
i) Fine structure mapping of chemical features of GPL
ii) Identification of the biosynthetic machinery for GPLs in
mycobacteria
iii) Retrobiosynthetic validation of fatty acyl chain component
of GPL
iv) Characterization of the position of hydroxyl group in the
structure of GPL
v) Genetic validation of the biochemical pathway using knock
out and complementation analysis
Research papers published: Nil
Papers presented in conferences : 4