‘While we think we understand the cell, it never ceases to surprise us’

6 Nov 2019

Dr Kabir H Biswas, assistant professor at the College of Health and Life Sciences at Hamad Bin Khalifa University. Image: HBKU

Dr Kabir H Biswas of HBKU is diving deep into our cells to find novel diagnostics and therapeutic interventions for a range of diseases.

Dr Kabir H Biswas obtained his masters and PhD in 2007 and 2011, respectively, as part of the integrated PhD programme at the Indian Institute of Science in Bengaluru, India. He then moved to the Mechanobiology Institute (MBI) at the National University of Singapore as a research fellow.

In 2016, he was appointed as an independent senior research fellow at MBI, before moving in 2017 to the Nanyang Technological University. He is currently an assistant professor at the College of Health and Life Sciences at Hamad Bin Khalifa University (HBKU), Qatar.

‘The fundamental challenge that we face is the astounding complexity of the cells that make us up’

What inspired you to become a researcher?

I think research came as second nature to me. I was regularly conducting ‘experiments’ during my childhood, thanks largely to my family and their continued support. For instance, I tried to cancel out the light emitted from a table lamp by turning on another bulb that I coloured black!

While this experiment failed, it did not stop me from continuing to think about how things work, and how we can manipulate things for the benefit of human beings and the environment. During school and my undergraduate studies, I was particularly fascinated by the protein machine that makes copies of the genetic material in our bodies.

The amazement continued during the latter stages of my higher education when I was exposed to how an individual cell in our body coordinates a myriad of biochemical processes, from generating energy to processing and mounting appropriate responses to all sorts of ‘signals’ that the cell experiences.

I was so engrossed in my studies that becoming a researcher was the obvious career choice for me. My teachers played an extremely critical role in this decision and I will always be grateful for their support and encouragement.

Can you tell us about the research you’re currently working on?

I am interested in understanding how cells in our body sense various external and internal signals, and processes them to produce highly specific and coordinated responses. I focus more on the biophysical aspects of cellular signalling, such as physical changes in the architecture of the cell and how genetic mutations in the proteins might alter these.

Recently in my career, I worked towards reconstituting cell-cell adhesion on synthetic supported lipid bilayers in a lab-on-a-chip format. Cell-cell adhesion is seen in a number of tissues and is key to the organisation of cells in the body.

We focused our efforts on the epithelial cell adhesion that is mediated by the protein called E-cadherin. Not only does it allow cells to attach to each other, this molecular assembly also enables the cells to sense mechanical tension in the tissue via structural changes in an adaptor protein called alpha-catenin.

We discovered that E-cadherin adhesion assembly into micron-scale molecular clusters is dependent on the molecular mobility of the protein on the cell membrane, a feature that’s currently unique to E-cadherin.

At HBKU, we are currently working on the reconstitution of cellular processes in a lab-on-a-chip format by incorporating precision biomaterials to control specific molecular assemblies and signalling pathways in the cell, as well as the generation of precision biosensors to monitor signalling events arising under a given perturbation.

We will be focusing on how cellular adhesion impinges on the cellular cytoskeleton, the basis of the physical architecture of the cell. We plan to perform genomic sequence analysis to look for mutations in the proteins involved in these signalling pathways in a large cohort of a designated population, and determine how these might cause or aggravate diseases such as cancer.

In your opinion, why is your research important?

I think a significant amount of research has been done in traditional areas of biology, including cataloguing proteins involved in a particular pathway and how these are biochemically altered in specific contexts.

These have certainly led to successful therapy for a number diseases. However, successful therapeutic intervention in multi-faceted diseases such as cancer requires innovative and substantially novel strategies. Our research efforts are directed towards this and will likely provide us clues to approaches towards precision medicine.

What commercial applications do you foresee for your research?

I think that our research has two possible commercial outcomes. First, discoveries that we make using our engineered experimental platforms could be utilised towards therapy for disease conditions such as breast cancer.

Second, we have developed a number of technologies that enable us to perform our experiments. These technologies could be commercialised for application in other contexts.

What are some of the biggest challenges you face as a researcher in your field?

The fundamental challenge that we face is the astounding complexity of the cells that make us up. First, it is composed of a large variety of biomolecules with different properties.

Second, unlike a bag full of stuff, many of these biomolecules are spatially organised in the cell. Third, these biomolecules often talk to each other in the sense that some of them can affect the function of others.

Therefore, while we take a reductionist approach in our experiments to understand cellular processes, we must realise that the cell is constantly integrating various kinds of inputs, some of which we know about and others we don’t.

While we think we understand a cellular process, take a look at it in a different way, and the cell never ceases to surprise us.

Are there any common misconceptions about this area of research?

A common misconception about our research concerns the relevance of the reconstitution experiments that we often undertake. I agree that the reconstitution of cellular processes using synthetic materials deviates from the in-vivo biological context. However, insights gained from these in-vitro experiments cannot be achieved using the whole organism.

Additionally, biophysical and quantitative approaches to biological processes is sometimes construed as challenging. But I can tell you that insights gained from these experiments are extremely useful.

For instance, measuring the rate of binding of a drug to a protein target, or a protein to another, could provide insights into a system that could be manipulated to achieve a desired outcome. In my opinion, implementing these insights into our biological science curriculum could decrease or remove this type of misconception.

Are you a researcher with an interesting project to share? Let us know by emailing editorial@siliconrepublic.com with the subject line ‘Science Uncovered’.