Prized Science | Decoding protein ‘interactions’, a hunt for elusive particles

Read about Shanti Swarup Bhatnagar awardees: Maddika Subba Reddy’s research on how proteins behave in cells and Anindya Das’ search for subatomic particles

Dr Maddika Subba Reddy, a cell biologist with the Centre for DNA Fingerprinting and Diagnostics, Hyderabad, works on the interaction between proteins in cells. His research earned him this year’s renowned Shanti Swarup Bhatnagar Prize which he shared with Dr Ashwani Kumar of CSIR-Institute of Microbial Technology, Chandigarh.

Dr Maddika Subba Reddy, a cell biologist with the Centre for DNA Fingerprinting and Diagnostics, Hyderabad

Read edited excerpts:

How do proteins “interact”?

Proteins are essential for every cell to carry out their functions in our body. Once they are synthesised in cells, proteins will carry out their functions by “talking” to other proteins via the complexes they form. Broadly, this is what my lab at CDFD is working on understanding.

As the old saying goes — “Show me your friends, and I will know who you are” — finding interaction partners for different proteins can reveal their function better in cells. This is what we do in the lab: finding interaction partners of different proteins in cells. Any alteration in the interactions between proteins can lead to disease. Therefore, to understand the reasons behind human disease development and progression, it is very important to understand the nuances of different protein complexes in cells.

Such as?

Specifically, we work on systems that maintain the fine balance in cells (cellular homeostasis). Once proteins complete their function, they need to be degraded in cells. Accumulation of proteins or damaged proteins is detrimental to the cell's health and leads to human disease.

Therefore, all cells have evolved a system called the ubiquitin system. Ubiquitin is a small protein that gets linked to proteins and acts as a signal for the attached protein to be recognised by degradation machinery in cells. We try to understand how ubiquitin gets linked to proteins, which is necessary for understanding the fine balance of protein function in cells.

Another system that cells have developed is the phosphatase system. Proteins in general are synthesised as inactive molecules in the cells. Once synthesised, they need to be modified to mediate their functions. Enzymes known as kinases add a phosphate group to the proteins, while phosphatases are enzymes that remove the phosphate group to maintain the balance of active and inactive proteins. Any disturbance in the balance of phospho-proteins is detrimental to cells and leads to various diseases such as cancers, neurological disorders, cardiovascular diseases etc. We try to understand how different phosphatases work in cells to maintain this balance.

How does this knowledge help in fighting diseases?

Our knowledge of how the balance between protein levels is maintained in cells while proteins carry different processes in our body is still nascent. Thus, a lot of work is needed to understand how proteins work, talk to each other, move from one place to another place in a cell and what systems regulate these processes in cells. The knowledge generated from our work will provide future therapeutic targets for different human diseases. While most pharmaceutical companies favour kinases to develop drugs against them, our work in phosphatases can offer them new and alternative targets for developing drugs for various diseases.

Hunting for Anyons

Anindya Das, associate professor of physics at IISc Bangalore

Anindya Das, associate professor of physics at IISc Bangalore, is one of the two scientists awarded this year’s Shanti Swarup Bhatnagar Prizes for Physical Sciences, the other being Basudeb Dasgupta of TIFR. Das works in the area of experimental condensed matter physics, specifically atomically thin materials and the quantum phenomena that come into play in interactions between such materials. In this interview, Das talks about these phenomena and the relevance of his work in the hunt for an elusive class of subatomic particles, called anyons. Read edited excerpts:

What are anyons, and why are scientists intrigued by them?

In the particle world, the elementary classes of particles are fermions (these include electrons and protons) and bosons, and distinct rules govern their behaviour. Anyons are a third category, which exist in theory but have not yet been discovered. Anyons lie somewhere in between fermions and bosons, with unique traits that are not found in other particles. These peculiarities hold the promise of potential use in quantum computing, particularly for topological quantum computers.

Anyons, which are confined to a two-dimensional plane, are a focus of study in condensed matter physics, notably within systems that strongly interact with each other, where they showcase their intriguing behaviour.

How is your work related to anyons?

Our work on experimental condensed matter physics focuses on transport phenomena in emerging quantum nano-devices. Quantum transport refers to the study and understanding of how electrons or other charge carriers move through materials at the quantum mechanical level. It is a branch of condensed matter physics that focuses on the behaviour of particles, such as electrons, in the presence of quantum mechanical effects, particularly in nanoscale systems or materials with unique electronic properties.

Detecting anyons in the lab is exceptionally challenging because they have fractional charges, and some are charge-neutral, making electrical current measurements nearly impossible to identify them. My group at IISc’s Quantum Transport Lab has made a significant contribution in this direction by developing a technique to measure the minuscule heat flows associated with anyons. To do this, we use a two-dimensional graphene sheet, with a thickness of 1 atom. Graphene and related materials, like twisted bilayer graphene, provide a natural two-dimensional platform for anyons at low temperatures. We have successfully detected heat currents for various anyons and are actively working to detect them for special anyons in the future.

What are the implications of this research?

Anyons hold the promise of enabling error-free quantum computing in the future. Quantum bits, known as qubits, are the building blocks for quantum computing, but qubits are highly susceptible to errors caused by factors such as interaction with the environment, thermal noise, and other forms of noise.

However, if anyons are used as qubits, they can be employed in quantum gates (a basic quantum circuit) by exploiting their braiding properties. Braiding refers to the exchange of anyons in various positions in a two-dimensional plane. The braiding of anyons is inherently fault-tolerant due to the nature of their topological properties. This would make them resistant to local errors.

The Shanti Swarup Bhatnagar Prizes for Science and Technology were awarded to 12 researchers in seven disciplines. The annual prizes, given by the Council of Scientific and Industrial Research, recognise scientists under the age of 45 for notable or outstanding research. This series will feature all 12 awardees