Taming pathogens to combat disease

Can Mathematical Modeling and Computational Fluid & Solid Mechanics be used to provide fresh insights into complex biological and medical questions?

Yes, says Amarender Nagilla, a research scholar with the IITB-Monash Research Academy, who is working on a project titled, “Modeling and simulations of construction and operations of interstitial networks in Pseudomonas aeruginosa” under the supervision of Prof Sameer Jadhav and Prof Prabhakar Ranganathan.

“Pathogens—clever fellows that they are—have learnt how to take advantage of the mechanical properties of their surroundings,” Amarender chuckles. “In many biological systems, there is a coherent motion of large populations of self-propelled particles. The collective motion makes them appear like viscous fluids, but unlike ordinary fluids, these are ‘self-propelled’.”

Amarender aims to develop mechanobiological models and simulations for systems such as advancing surface swarms of bacteria, and hopes that this could help uncover novel mechanical strategies to control the spread of bacterial infections in medical implants.

The IITB-Monash Research Academy is a collaboration between India and Australia that endeavours to strengthen scientific relationships between the two countries. Graduate research scholars like Amarender study for a dually-badged PhD from both IIT Bombay and Monash University, spending time at both institutions to enrich their research experience.

“Many pathogenic bacteria colonise interstitial spaces between tissue surfaces. When they reach a sufficient density, they appear to use a range of collective strategies to spread quickly as a monolayer to lay the foundations for a mature biofilm,” explains Amarender. “It has been recently shown in Pseudomonas aeruginosa colonies growing between agar and glass that cells at the edge of advancing colonies self-organise into distinctive networks of trenches as they plough through the soft agar (a jelly-like substance, obtained from algae). Cells behind these rafts secrete extracellular DNA which appears to regulate traffic to ensure a smooth supply of cells from the colony interior to the advancing edge. A fingering instability of the edge of the bacterial monolayer as it ploughs its way through the soft substrate might explain the emergence of cell rafts.”

To prove the hypotheses, says Amarender, computational models are required. It would be difficult—and computationally very expensive—to build 2D and 3D models with all the possible details filled in. He is convinced that the solution is to build minimal computational models based on specific requirements. “What excites me most is the opportunity to develop one-dimensional (1D) models with simple resources which could produce results similar to 2D models. Our models would be computationally cheap but robust. They could be used across different systems—including biological systems—like propagation of different types of cells, bacterial colonies, migrating herds, and non-biological systems like interfaces of multi-phase fluid flows.”

Says Prof Murali Sastry, CEO of the Academy, “Today’s research challenges require a strongly multi-disciplinary approach. And the way in which the IITB-Monash Research Academy has been set up makes it very possible for such multi-disciplinary investigations to be carried out. This gives me immense hope that the Academy will create significant science, societal and industry impact in the future.”

Like pathogens, researchers like Amarender are imbibing ways to take advantage of the emerging and highly interdisciplinary field of computational bioengineering, in order to advance fundamental understanding as well as develop new computational techniques in the quest to combat disease!