What it looks like... determines what it does. In other words, the structure of a biomolecule determines its function. We aim to understand the function of biomolecules by combining results obtained using various techniques such as molecular biology, X-ray crystallography, biochemical and biophysical studies and computational biology. Currently, our focus is on the following research areas.

Protein translation initiation
In bacteria, the process of protein translation can be roughly divided into three main stages namely (1) initiation (2) elongation and (3) termination. The initiation of protein translation requires the ribosome to position a unique tRNA (known as initiator tRNA or fMet-tRNAfMet) over the start codon (usually AUG) of mRNA in the P site. The positioning of the ribosome is primarily anchored by base pairing between the 3′ end of 16S RNA and a complementary sequence, upstream of the mRNA start codon (known as the Shine–Dalgarno sequence). In bacteria, three initiation factors (IF1, IF2 and IF3) along with the special initiator tRNA help in the precise positioning of the start codon in the P site of the ribosome. In eukaryotes, the protein translation initiation requires approximately 9-12 initiation factors. In contrary to bacterial systems, in eukaryotes, the initiation comprises of two steps. Firstly, the formation of 48S initiation complexes (IC) consisting of 43S pre-initiation complexes (PIC: 40S ribosomal subunit, eIF2-GTP-fMet-tRNAfMet and probably other initiation factors) and the established codon-anticodon base-pairing in the P-site. In the second step, IC joins with the 60S ribosomal subunit. On most mRNAs, 48S complexes form by a ‘scanning’ mechanism, whereby a 43S PIC attaches to the capped 5′ proximal region of mRNAs. Although most mRNAs use the scanning mechanism, initiation on a few mRNAs is mediated by internal ribosome entry sites (IRESs). However, exactly how the correct tRNA during the initiation and elongation stages of protein translation is selected and/or differentiated remains unclear, as are the roles of the various factors. The mechanism of protein translation initiation is still not clearly understood owing to a paucity of structural data.

Drug development against human pathogens
Currently, we are working on various targets from human pathogens for drug development process. One of the targets belong to the nutrients uptake systems, particularly in pathogens. Furthermore, our focus is on the systems maintaining the bacterial membrane, especially under harsh environmental conditions. Several mechanisms have been proposed that modulate membrane permeability in normal as well as stress conditions. We are trying to understand the mechanistic insight of an ABC transporters which regulates membrane kinetics.

Understanding mechanism(s) of (multi)drug resistance
Antibiotic and drug resistance is a phenomenon of crucial importance in the treatment of diseases caused by pathogenic microorganisms. Bacteria have evolved various strategies to evade the cytotoxic effects of antibiotics/drugs. One of these stragies is alteration of the antibiotic binding sites by enzymatic modifications. Nature has evolved an effective and elegant ways of preventing drug binding to the ribosome , one of them is by adding methyl groups to ribosomal RNA at appropriate sites. In addition, several pathogens have developed systems which can protect them from host-produced antimicrobial peptides.