The Small Molecule Biology Lab. is involved in understanding the biological role of small molecules. We study their roles in metabolic pathways and as second messengers in signal transduction pathways in the homologous biological systems.
In heterologous systems, we study their role as bioactive molecules. The underlying platform includes a combination of analytical technologies such as chromatography coupled with mass spectrometry, functional genomics technologies such as gene microarray and proteomics and integrated with in-house developed computational and bioinformatics tools.
Hence, we combine wet and dry laboratory work within our group. Our model organisms are diverse and include bacteria (Bacillus, Pseudomonas), Arabidopsis, rat and human skin cells. We have developed capabilities to comprehensively map out the changes in the metabolic complement or the 'metabolome' of cells in response to perturbations such as metabolic mutations, effector molecules, or stresses. This approach has allowed us in various projects to:
- Uncover some broad connections in metabolic networks;
- Describe novel microbial catabolic pathway;
- Identify members of novel family of bioactive compounds;
- Propose a 'rhizosphere engineering' approach to increase competitiveness of soil microbes;
- Identify groups of co-regulated genes associated with the 'metabolome'.
We are currently taking a systems approach to understand metabolic networks and their perturbation by diverse intrinsic or extrinsic signals in plant and animal models.
We have recently described the regulatory mechanism for a novel cyclic nucleotide 2nd messenger in microbes, cyclic-di-GMP. The regulator MorA is especially conserved in Pseudomonas, it synthesizes as well as hydrolyses cyclic-di-GMP and controls more than 150 genes in pathways such as motility and biofilm formation. Another small molecule, acetyl phosphate, acts as a cofactor in this process. Current efforts in the laboratory are focused on the elucidation of the structure, function and regulatory circuit of the pathway. |