Researcher profile: Suparna Sanyal

‘There’s been a common belief that if you want to engineer bacteria, don’t put your hand in the ribosome operon. All my teachers told me ‘don’t mess with the ribosome’,’ says Suparna Sanyal and laughs. Since then, her research team has successfully produced advanced bacteria that facilitate the purification processes in ribosomes, potentially leading to more effective medicine.
^{Photo: Mikael Wallerstedt}

Master of molecular mechanisms

Ever since her childhood in Kolkata, India, Suparna Sanyal has wished to understand why we get sick and how medicines work in the body. Today, her research unravels the molecular mechanisms of protein synthesis and protein folding.

’In the future, this knowledge might lead to new pharmaceuticals such as antibiotics against drug-resistant microbes or medicines against prion diseases,’ says Professor Suparna Sanyal at the Department of Cell and Molecular Biology, ICM.

When Suparna Sanyal began her undergraduate studies at Bethune College, Kolkata, she was unsure of what path to choose. She ended up taking undergraduate courses in zoology, chemistry, botany, physiology and genetics. The latter stimulated her learning appetite, and a teacher directed her to a new area of advanced study: molecular biology and biophysics.

‘This field was only taught at one department at the University of Kolkata. The Department of Biophysics and Molecular Biology admitted just about ten students a year so the competition was fierce,’ says Suparna Sanyal. ‘The students were extremely bright; they went on to doctoral studies and positions at prestigious universities. So I knew I simply had to study molecular biology.’

It worked out; she got accepted. Her studies went smoothly and resulted in a master degree in biophysics, molecular biology and genetics, followed by doctoral studies in protein folding problems at the same institution. However, soon she started to feel there was a link missing between medical practice and basic research.

‘The physicians I met at the hospitals understood very little of what was happening at the molecular level. This was something I couldn't understand: how else will you know if the medicine you are going to use will work? I wanted to go into proper, basic research and use it to discover new medicines.’

When Suparna Sanyal first heard of Uppsala University, it was for its strong research environment in biomedicine. However, her first stop in Sweden became the University of Lund, where she arrived as a postdoc in 2000. Two years later, she acquired a position as assistant professor at ICM.

‘Uppsala is a fantastic place for molecular biological research, especially the focus on protein synthesis, antimicrobial resistance and RNA biology. In addition, all are very collegial,’ says Suparna Sanyal and smiles.

Today, she has got her own research group with a focus on protein synthesis and protein folding by the ribosome. This is the large RNA-protein complex inside the cell that translates the genetic code into functional proteins. Her group mainly uses bacteria as a model system as such studies may help fight serious antibiotic-resistant bacteria, including those causing tuberculosis.

‘Studying bacterial protein synthesis is very important as it allows us to find differences between our cells and bacterial cells. In addition, we’re able to study how cells can withstand stress in various forms. These differences we can then use to select, block and kill bacteria with the help of antibiotics.’

Her research group has recently developed a method for production of proteins in the test tube by combining more than 50 purified components from bacteria E. coli. The method called RTTF (Reconstituted Transcription Translation Folding) has managed to produce proteins from DNA or RNA with very good results, according to Suparna Sanyal. In another project, she and one of her postdocs have designed a bacterial strain, JE28, in which the ribosomes are fitted with tags of the amino acid Histidine, called His-tags. The strain has been named after the postdoctoral researcher, Josefine Ederth.

‘The JE28 strain has become really popular and we have sent it to more than 100 labs around the world. Using it saves an enormous amount of time and material for the purification of ribosomes. With the usual methods, it takes several days to purify ribosomes, but with JE28 it takes an hour.’

Another goal for Suparna Sanyal is to find the causes of the misfolding of proteins, which can lead to prion diseases like the mad cow disease and Creutzfeldt-Jakob disease. Her research group has shown that the protein folding activity of the ribosome (PFAR) can be involved in prion propagation.

‘Prion proteins are found in nerve cells. When proteins misfold and build up amyloid fibrils, the neurons are prevented from performing their work. That’s why you develop dementia, or maybe start losing your balance. But if we can understand the mechanism, we can also find ways to stop the process.’

According to Sanyal Suparna, the search for effective medicines must also get more organized.

‘I often think diseases are treated using "trial and error". A medicine is tested and if it doesn’t work, another one is tried out. But without having a molecular understanding of functions and structure, the medicine is incomplete. If one day it no longer works, well, then you’re stuck and cannot improve the formula. That’s why we need to do even more research on the mechanisms of molecular biology.’

 Anneli Björkman