What is biofilm, the subject of your research?

Bacterial biofilms are communities of bacteria that are held together by a matrix that the bacteria make themselves. The nature of the matrix is the Holy Grail for scientists seeking to understand these communities and the bacterial behaviour in them. Bacteria are social organisms, and to make these communities is their natural way of life.

Microbiological studies, however, are largely built on growing bacterial cells as single-cell suspensions. Studying bacterial cells in such suspensions offers several advantages for understanding bacterial physiology, but, at the same time, we are then studying them in an unnatural state.

The capability of pathogens to make biofilms gains particular relevance in the case of chronic infections. This is because these biofilms act as castles or bunkers wherein the bacterial cells can remain hidden from the immune system and antibiotics.

What is the role of biofilms in tuberculosis?

Textbooks describe the Mycobacterium tuberculosis (Mtb), the causative agent of the disease, as an obligate intracellular pathogen. This term refers to pathogens that need a host cell to reproduce and survive. This notion about Mtb is based on observations that the bacterium is often seen inside the macrophages (a certain type of cell) of the infected person.

Because of this notion, scientific studies have largely ignored the capability of Mtb cells to form biofilms. Being large structures composed of several bacterial cells and extra polymeric substances, biofilms cannot usually form inside cells like macrophages, which are much smaller. Thus, generally, extracellular bacteria make biofilms.

Although Mtb is defined as an obligate intracellular pathogen, a large number of Mtb bacilli are also observed in the extracellular spaces in the infected lung. This is where it becomes interesting to test the possibility that Mtb could make biofilms in these spaces outside of the host cells.

And, you have found that Mtb does make biofilms?

My laboratory has earlier described that reducing stress (something that inhibits the growth of bacteria), which is present in the lung environment, induces Mtb to form biofilms. We have also demonstrated that Mtb cells utilise cellulose, a polymer often found in plant cell walls, to make these biofilms. Furthermore, inside these biofilms, Mtb becomes unresponsive to anti-TB agents.

What is the way to fight this?

We have demonstrated that cellulase, an enzyme, could disintegrate the Mtb biofilms and make the bacteria susceptible to drugs again. We carried out experiments that suggest that in some cases of human tuberculosis, Mtb cells are present encased in biofilms. We have performed experiments in mice infected with Mtb and found that administering nebulised cellulase helped anti-TB drugs kill Mtb during infection.

Dark matter rising

At TIFR, Mumbai, physicist Basudeb Dasgupta studies, among other things, the interface between particle physics and astrophysics. His theoretical work on subatomic particles called neutrinos, which straddle both the atomic and astrophysical worlds, and the mysterious “dark matter” earned him this year’s Shanti Swarup Bhatnagar Prize for Physical Sciences, shared with Anindya Das of IISc Bangalore. In this interview, Dasgupta describes what his studies have taught us.

How do you connect the physics of astronomical bodies with particle physics?

Just as understanding atoms helps us understand the chemistry and properties of unusual materials, understanding particle physics helps us understand the behaviour of astrophysical objects (and vice versa). To take an example, stars harbour extreme temperatures and pressures where many exotic subatomic particles are produced. These particles, in turn, affect how the star evolves by burning its nuclear fuel. Thus, understanding the new particles allows for understanding stellar evolution better. By the same token, if we understand how a star burns its fuel, any departure from this understood pattern, if observed, would raise the possibility of discovering new particles and effects that presumably are causing the departure.

What has your research on neutrinos taught us?

Neutrinos exist in different kinds, known as flavours, and are known to change from one flavour to another. Inside massive stars, this process is predicted to speed up in certain situations, which are known as an “instability”. This instability occurs due to the coherent interactions of many neutrinos with one another in a densely packed environment. We have mathematically proved that a specific condition needs to be satisfied for the instability to happen. We have predicted that this can indeed occur deep inside stars. This, in turn, is believed to affect the explosion of the star and the creation of chemical elements essential for life in the universe.

What is dark matter, which has been theorised but not yet been fully explained?

Observations of galaxies, clusters of galaxies, and the universe at its largest are at odds with theoretical predictions. These objects have spinning and jiggling motions that can only be explained if they contain more mass than is apparent. This extra mass must be in the form of a new kind of matter that interacts very rarely, if at all, with light or ordinary atoms. Discovering the elementary constituents of this so-called “dark matter" is a frontline goal of modern science.

What has your research in this field been?

We analyse possibilities for the microscopic nature of dark matter using theoretical physics, mathematics, and computers. The work involves writing possible "models", calculating its consequences, and comparing these predictions with observations by specialised telescopes of international teams.

Among the possible dark matter candidates are black holes of very low mass. Although these have not yet been ruled out, our work has put strong constraints on the fraction of dark matter that can be attributed to very low-mass black holes.

In other work, we have predicted novel signatures of dark matter accumulating in stars. While these studies do not yet tell us what dark matter is, they do tell us what it is not, and can steer future efforts in more useful directions.

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. Read interviews of all 12 awardees in the Prized Science series