Angelina Tan Wei Ling

I am working on the isolation and characterization of anticoagulant proteins from salivary gland extracts of ticks.This involves purification and structure-function studies of the novel proteins.

Sindhuja Sridharan

I work on a novel Natriuretic peptide (NP) identified from the transcriptome of krait, called KNP. Although KNP has evolutionarily conserved residues responsible eliciting function, it has a distinct C-tail compared all other known NPs. In my doctoral study I'm interested in investigating the structure function relationship and action mechanism of KNP.

Ritu Chandna

The growing interests in nicotinic AcetylCholine Receptors (nAChR) are because of their their involvement in several important CNS pathologies. These membrane proteins appear to be highly heterogeneous and still only little information is available in their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions. Snake venom is a good source of these ligands and my project aims at characterization of 3 novel three-finger toxins (3FTxs) identified from the snake Dysdalia coronoides venom gland. Drysdalin, the longest of all the 3FTxs identified does not possess the functionally important residues and has a long C-terminal tail predicted to form ? - helix. Functional characterization of drysalin shows that it is a postsynaptic neurotoxin and irreversible antagonist to muscle nAChR, only 2.8-fold less active that the potent ?-bungarotoxin. Nanomolar toxicity even in the absence of functionally important residues may be attributed to the long C-terminal tail. Hence the functional and structural characterization of the C-tail truncated drysdalin is warranted. The other 2 novel 3FTx513V and 342 also lacks few of the functional important residues and it is interesting to study if these changes have occurred to bind to a new subtype of nAChR.

Bidhan Nayak

I am working on the structure-activity relationship of a Phospholipase A2 enzyme from S. violaceoruber, with the aim to design a small active scaffold of the enzyme.

Summer Han Xia

I'm studying the transcriptional regulation of Trocarin D from Tropidechis carinatus. To understand the transcriptional regulation, I will identify the DNA cis-elements and interacting protein transcription factors which regulate the expression of Trocarin D.

Varuna H.P.

Nicotinic acetylcholine receptors (nAChRs) mediate ionotropic actions of acetylcholine in the central and peripheral nervous system. Due to the lack of highly selective nicotinic ligands, the precise location, functional roles and various disorders associated with nAChRs remain unclear. Neurotoxins isolated from snake venom have a natural high affinity and selectivity to nAChRs, which act as competitive antagonists, allosteric modulators and potential agonists of nAChRs. These neurotoxins may therefore be invaluable tools for studying nAChRs. In my study, a novel recombinantly expressed 3FTx with His-tag is found to be postsynaptic reversible neurotoxin on ex-vivo neuromuscular junction and binds to rat muscle-type (?1)2?1?? and to rat neuronal ?4?2 and ?3?2 nAChR but has no affinity towards human ?7 receptor.

The structure-function relationships of the 3FTx will be further investigated with series of mutants using site directed mutagenesis approach in order to delineate its interaction sites.

Iyer Janaki Krishnamoorthy

My project focuses on identifying and characterizing anticoagulants from hematophagous animals. These include inhibitors of key players of the blood coagulation cascade like thrombin and factor Xa. The salivary gland extracts of ticks show very potent inhibitors of these enzymes. These inhibitors are present in extremely low amounts in the salivary gland extracts of these ticks. Therefore, these cannot be purified by the traditional analytical chromatographic techniques. Towards this, I have developed a miniaturized workflow for on-line post-column identification of thrombin and fXa inhibitors. In this miniaturized workflow, purification is first performed via nano liquid chromatography and this is coupled to an on-line assay which takes place inside a microfluidic chip in parallel with the mass spectrometric identification of the compounds. This technique is actually a rapid screening technique to identify such inhibitors from complex mixtures. Therefore, we have developed a miniaturized workflow for on-line post-column identification of thrombin and fXa inhibitors. In this miniaturized workflow, purification is first performed via nano liquid chromatography and this is coupled to an on-line assay which takes place inside a microfluidic chip in parallel with the mass spectrometric identification of the compounds. I am working further towards the identification of these compounds from the salivary gland extracts of hematophagous animals.

Norrapat Shih

My project focuses on pre-clinical studies of Variegin, a very potent anticoagulant peptide isolated from the tick salivary gland. Our plan is to push this peptide into clinical trials, and eventually bring it to the market. More specifically, I am interested in studying the pharmacokinetics and pharmacodynamics of this peptide. With this knowledge, we will understand the stability of this peptide drug in-vivo and thus know the dosage required to give to patients. Furthermore, I am also interested in selecting for DNA aptamers that can bind to Variegin as an antidote.