My research interest revolves two "diverse" themes:
- MODULAR APPROACH TO STUDY FUNCTION AND EVOLUTION
- MANAGEMENT AND STRATEGY ISSUES IN THE BIOTECH SECTOR.
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Modular Approach to study function and evolution
The drug discovery process would be helped by information on roles played by complete
functional units, reactions they catalyze and residues responsible for the specificity.
This information comes at the gene product level. There are number of domain classification
systems, though they are very useful for structure prediction, they have limitations when it
comes to function prediction. Also available are resources, which aim at classifying protein sequences from
publicly available databases like UniproT and Genpept into sequence level
super-families, aiming to reciprocate SCOP at the highest level of hierarchy.
Nevertheless, two key issues remain an open puzzle, firstly automated function prediction
of multi-domain proteins and an automated hierarchical functional classification system
using only sequence data.
We are addressing these issues by proposing what would be a “modular” classification of the
protein universe. Contemporary proteins exist either as composite (A protein which exists as fused
gene in one or more genomes, while occurring as two or more separate homologous genes in other genomes)
or component (A complete functional protein which exists as one component of a fused gene in another genome).
Many composite proteins seem to be a product of unrelated gene fusions. In other words they are made by
fusion of two unrelated component proteins. Here we propose an evolutionary scenario, where proteins
evolved as component proteins and hypothesizing that the function of fused genes [composite proteins]
are defined either by the interaction between their component proteins or as multi-functional
(combination of gene products).
Our understanding and basis of the new concept comes from study of mechanistically diverse super-families like
the crotonases. The crotonases (Enoyl CoA hydratase super-family)represent a diverse set of proteins sharing
a common structural scaffold at a super-family level and a common catalytic strategy by catalyzing reactions
that usually involve a thioester enolate anion intermediate stabilized by hydrogen bonding with two peptidic
NH groups in an oxyanion hole. The crotonase sub-classes diversify to catalyse different overall reactions.
There have been extensive studies on individual enzymes proposed to belong to this remarkable super-family.
We performed the first comprehensive study on evolution of functional repertoire in multiple members of this super-family.
Here we studied the diversity of crotonases in the bacterial and archaeal genomes.
These studies helped us addressing key issues like defining sequence level super-families, defining meaningful
sub-groups within super-families, characterizing putative functional fingerprints and residues.
We have recently demoposed the complete set of sequences from complete genomes into a non-redundant set of
modules. We call this set as "Module Space" which is available for download. A classification of module space
into super-families of homologoues sequences is currently under development. We are actively researching
on using module space to address fundamental biological questions having biomedical relevance. Module space
is based on enumerating and charecterising gene fusion (the term is used broadly in this context: please refer to
related manuscripts) events. We are interested in studying the following key questions in detail.
- Does the fused gene develop a new function different from their constituent component proteins?
- Gene fusion as an effective approach to enumerate new protein-protein interactions.
Management and strategy issues in the Biotech sector
One of my parallel areas of interests along with the scientific themes
which Iam addressing is a key area which can be broadly classified under
the specialist area of "knowledge dissemination".Strategies adopted for
disseminating knowledge is a key to interface Science, Technology and
Society which in turn decides the economy of the field. Some of the key
areas of my interests are:
- Management and marketing strategies within organisation types
- Organisational strategies and issues
- Maximising the potential of e-commerce in the Biotech sector
I have finished writing a series of vision articles on these issues,
some of them will be available in open source. Please do not hesitate
to contact me if you wish to collaborate on any of my interest themes.