You are here

Molecular Biophysics Unit

  • Photograph 51, considered "the most important photograph ever taken". In 1953, Rosalind Franklin used X-ray crystallography to produce images from a crystal of DNA. This photograph was a critical piece of evidence that led Watson and Crick to describe the structure of DNA. The technique of X-ray crystallography is being used in all three Divisions. To commemorate a century of use of the technique, 2014 was declared The International Year of Crystallography. The Indian government has also released a stamp (inset).

Images adapted from Wikimedia Commons.

From the genetic blueprint in their DNA, living beings make proteins that carry out various functions. As far as molecules go, proteins are rather large. They are made of repeating units of amino acids. The sequence of amino acids in a protein is determined by the stretch of DNA that codes for the protein. The amino acid units in a protein chain interact with each other, and with amino acids in other chains, to form structures varying from simple chains, to braids, to large globular structures.

Saraswathi Vishveshwara uses mathematics and computational techniques to understand how proteins fold into complex structures, and how the structure formed performs the designated function.

 Lectins are proteins that bind to carbohydrates in a very specific manner. Molecules use them for recognising each other -  in some cases bacteria and viruses decide how and who to attack by using the carbohydrates  on targets. They also help targets recognise the infection and mount an immune response. Lectins arefound in many different organisms, and M Vijayan in collaboration with Avadhesha Surolia has been studying lectins in peanuts, jackfruit and banana, amongst other plants. He has also been working on figuring out the structure of different proteins in Mycobacterium tuberculosis, the bacterium that causes the dreaded TB. Avadhesha Surolia also works on the design of drugs against malaria, on delivery of DNA and drugs to cells, and on treatments for various chronic diseases such as arthritis and diabetes.

Padmanabhan Balaram’s research focuses on peptide design, protein structure, and interactions between proteins.

If proteins in disease causing microbes are studied, it can help in designing drugs that can target specific proteins and render the microbe ineffective. In MRN Murthy’s lab, the three dimensional structures of three proteins from the malarial parasite, Plasmodium falciparum, were determined. Salmonella typhimurium hops on to humans from infected meat, causing food poisoning and gastro-enteritis. In mice, S. typhimurium causes symptoms resembling typhoid fever in humans. Studying these bacteria in mice could eventually lead to a typhoid vaccine. The lab has characterised and crystallised a key enzyme essential to microbes - a potential drug target.

DNA occurs most commonly in one form - the one Watson and Crick hit upon when they discovered its structure. However, there are some unusual forms that occur in nature. Manju Bansal uses computer models and simulations to study unusual DNA structures.

Dipankar Chatterji’s group has been working on bacteria to understand the puzzle of gene regulation. The lab is working on using Mycobacterium smegmatis under nutritional starvation as a model system for latent M. tuberculosis.

Neurons are specialised cells that can transmit information through electrical and chemical signals. S K Sikdar has been studying how these cells use passageways in their cell membrane to move charged metal ions to transmit electrical signals. He also works on the mechanism by which neurons line up to form intricate networks that spread throughout our bodies. Rishikesh Narayan has been working on information processing in both single neurons and networks, using both experiments and computational analyses.

Using a variety of tools like spectroscopy, crystallography and computational procedures, Raghavan Varadarajan’s lab is trying to understand the basics of how proteins fold into three dimensional forms, and how they remain stable. One of the current projects is to stabilise one of the proteins in the outer membrane of HIV, the virus that causes AIDS. The protein is very unstable; if they can succeed in stabilising it, it can be used in a vaccine to generate antibodies that protect against HIV-1 infection. K Suguna’s specialisation is crystallising proteins, and she collaborates with other faculty in MBU and other departments to use her expertise. She has worked on a variety of bacterial, viral and malarial parasite proteins.

Siddhartha P Sharma uses Nuclear Magnetic Resonance spectroscopy to study protein structure and interactions between proteins. They are especially interested in naturally occurring protein toxins found in marine snails. 

The cells in our bodies have proteins embedded in their outer membranes, which act as gatekeepers that allow desired traffic to pass. They also act as markers that communicate to other cells if there is a foreign body like a microbe inside, for example. B Gopal studies both membrane proteins and water soluble proteins using biochemical, molecular biology and crystallographic techniques.

Jayanta Chatterjee focuses on developing a better cancer chemotherapy drug, by targeting protein interactions inside cancer cells using small protein chains called peptides, which will potentially have lesser side effects. The lab is also working to improve the stability of these peptides so as to increase their lifetime inside the body.

Papers:

Bacilysin is a potent antibiotic which scientists have been trying to synthesise in the lab for the last 30 years. M Rajavel and Kumar Perinbam from B Gopal’s lab added an important piece to the puzzle by characterising one of the two proteins that make up the antibiotic (Acta Crystallographica Section D: Biological Crystallography; doi:10.1107/S0907444912046690).

Krishnayan Basuroy and others from Padmanabhan Balaram's lab worked on monosubstituted, unconstrained gamma residue, Gamma4Valine . They have modified the backbone of the proteinogenic (genetically coded) residue, valine by inserting two additional atoms on the backbone and successfully introduced the residue in alpha-gamma hybrid peptide sequences. They have also crystallised the peptides and succefully recorded the X-ray diffraction data for those. Properly refined X-ray data for the alpha-gamma hybrid peptides revealed well folded helical structures even in the absence of any helix inducing, stereochemically constrained gamma residues - a breakthrough in protein engineering research (Angewandte Chemie International Edition; doi: 10.1002/anie.201209324)

The hippocampus is a brain region responsible for learning and memory. Pyramidal neurons present in the region have extensive projections called dendrites, which regulate the properties of the neuron. Using computational models, Anindita Das and Rishikesh Narayanan found that membrane gateways called ion channels in the dendrites determine information processing by the neuron. There can be a lot of variation even within a single neuron, and with the variation in inputs from the external environment as well as the location of inputs on the dendrites/neurons. The study uses quantitative tools to understand how changes in a single neuron changes the way information is processed during learning and memory encoding.

Tag: 
MBU