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FNR ATTRACT FELLOWS: Anupam Sengupta THE PEOPLE BEHIND THE SCIENCE

Anupam Sengupta went from being an engineer in India to studying physics in Germany, before diving into biology in the US and Switzerland. Combining his expertise in these fields, the Indian national came to Luxembourg in 2018 with an FNR ATTRACT Fellowship to set up his research group at the University of Luxembourg as a tenure track Professor in Physics. We speak to the biophysicist about his journey and passion for uncovering the secrets of how the smallest of living organisms regulate our health and happiness, and get impacted by the changes in their environment.

Your research field – biophysics – combines biology and physics. Is your field new, or has it changed?

“The field of biophysics, in general, itself is not new – though the questions we are starting to ask are.

"We now have access to techniques that allow us unprecedented insights into the living world, in real time, from single cells to multicellular organisms. We have better imaging and image analysis techniques, high-end computing platforms, and a cross-disciplinary mindset that allow us to study processes not only in detail and overlong timescales, but crucially, in a quantitative multi-pronged manner.”

How do you combine biology and physics?

“As a physicist, you are used to number crunching whenever you have access to data. When you have the numbers, you can start to see patterns in a quantitative way, and propose a framework that could explain the pattern. I would say this approach when applied to study living systems is what biophysics is all about."

"The beauty of the approach is that you can test your framework against your working hypothesis: if this fits – EUREKA! And if not, we can still revise the framework iteratively, till we reach a reasonable, if not complete agreement with the experimental data that could explain the observed patterns.

“Traditionally, biology takes a more empirical approach, in the sense that you have a phenomenon, you observe trends and patterns, and you leave it there. As biophysicists, we not only extract those trends and patterns, but we also try to use that to model the system, so that we can hypothesise future events, and predict future scenarios and then test our model against experiments that simulate these future scenarios. This iterative approach, in the longer run, should help us uncover principles underpinning biological processes and systems."

“What is also important is the effect of any change in the parameter or the environment of the system. How would the system respond and adjust its behaviour?

"That’s where biophysics comes in: we can look for and use principles from physics to develop working models, and propose improvements to existing ones."

"We can change the variables in the model and then get a first insight about how the system could respond, and follow it up through experimental validation. This way we get an iterative view, which over multiple sequences help to adapt both the modelling and experimental protocols, ultimately giving us a better grasp on the behaviour of the system.”

“In short, we study living matter systems: we extract multi-dimensional data using high resolution visualisation techniques and map them to microbiological and molecular readouts. Once we have this holistic information, we are in a robust position to fully understand the system at hand."

What kind of questions do you ask?

“The questions or the problems we deal in our lab all are, in general, at least in part motivated by the changes in our environment and their impact on microorganisms and their consortia. On the one hand these could be climatic shifts that we are all growingly concerned about, and on the other, could be due to changes in our lifestyles that could restructure microbiome associated with different organs."
"We generally see impacts on a larger scale, but what we often end up neglecting and ignoring is the consequence of these changes on some of the tiniest organisms at the base of our ecosystem. These organisms, including bacteria and algae, are not visible to the naked eye, yet they play crucial roles in regulating and holding our ecosystem in a balanced state."

"Algae, for example, are photosynthetic microorganisms which process sunlight to generate 50% of the oxygen we breathe, and in doing so, absorb enormous volumes of atmospheric carbon dioxide."

“Climate change, which can e.g. be due to changes in the temperature, or light conditions, have cascading impacts. Take for example the bush fire in Australia at the beginning of this year: It drove many species from their natural habitats, restructuring the ecological networks formed by those species. A similar scenario plays out if you scale things down to the dimension of the microorganisms."

"Restructuring of microbial networks due to anthropogenic factors can have significant implications for global biogeochemical cycles, microbiomes associated with plants, animals and humans, and ultimately, of the entire ecosystem spanning multiple scales. In my lab, we have started to track these dynamical processes systematically through a combination of experiments and data-based modelling.”

You for example look at what impact changes in the environment have on small organisms. Which aspects do you observe?

“Broadly, we study two sets of microbial systems: Aquatic and marine microbes, where the impact of climate change is profound; and the bacterial consortia resembling the gut environment. Despite the seeming disparity, the two systems have surprising similarities, not least in the biophysical principles underpinning the systems.
"Luxembourg is highly active in the gut microbiome research, and my lab is part of one of the FNR PRIDE Doctoral Training Units, (MICROH)."

"We bring a biophysics approach to the DTU, and aim to develop a principle-oriented understanding of how microorganisms interact in such dynamic environments. Going beyond the aquatic and gut environments, we expect the results from our research could be generalised also for other microbial systems, for instance the microbiome of the skin, the oral cavity, or the soil, because the general principles that guide and dictate the dynamics should remain conserved across systems.”

You originally come from the field of engineering and physics. How did you make the connection to biology?

“Back in India, I graduated in Mechanical Engineering from the Indian Institute of Technology Bombay (in Mumbai). At IIT, we had a running gag that everything under the sun can be tackled through mechanical engineering. At the time this was an amusing reference, but as time passed, it did turn out that my specialization in thermodynamics and fluids engineering provided a robust backbone to my cross-disciplinary training.

"Right after my undergraduate studies, I moved to Germany, where I spent time at an engineering start-up developing thermo-fluidic solutions, though I missed the challenges and excitement of research."

"After about a year, I changed tracks to Physics and joined the Max Planck Institute for Dynamics and Self-Organization as a Marie-Curie Doctoral Fellow. As I entered the world of physics during my PhD studies, I quickly learned that for a physicist, the focus is ‘to develop a fundamental understanding’ – which for me was a new way of asking questions, a bit in contrast to engineering studies."

"Synergies came up with biology during the final stages of my PhD studies, and it was during this time that I had the vision for the ATTRACT research project, which I am now doing in Luxembourg. However, to realise the vision, I first had to get trained as a biologist. Luckily, I was awarded the Human Frontiers Cross-Disciplinary Fellowship, that took me to MIT and then to ETH Zurich, where I could pick up valuable skills in biological research as a biologist.”

Your research field is interdisciplinary in nature, can you tell me about the composition of your research group?

“We are a truly interdisciplinary team, spanning both experimental and theoretical expertise in microbiology, physics, engineering, chemistry and mathematics. Each of my group members has their own project playing to their expertise, but there is a thread connecting all of the projects."

"Consequently, we have an extremely dynamic exchange of ideas, where everyone is learning many additional skills from each other’s projects, while drafting their individual breakthroughs. This makes the Sengupta Lab a truly vibrant research setting to work in.”

You are a big proponent of combining expertise from different fields. Having covered engineering, biology and physics, do you feel comfortable in all fields now?

“Today, the major challenges ahead of us, are all inter-disciplinary in nature. It’s crucial for a PI to speak languages that help to connect the relevant disciplines, quite in line with the multi-lingual spirit of Luxembourg. I now feel comfortable speaking to biologists, though you have to ask my biology colleagues if they feel comfortable speaking to me! Often as physicists you run the risk of sounding too technical, and thus being left out due to a missing biology ‘jargon’. I think there is now a conscious effort from both sides – physicists and biologists – to understand each other."

"The next breakthroughs in the grand challenges of physics will likely come from biology. On the other hand, biologists clearly see the value of numbers and patters and how you can use these to understand living matter systems. And the trend is getting stronger, especially here is Luxembourg with numerous initiatives emerging both at the levels of research collaborations across labs, and institutional initiatives like the Physics Meets Biology initiative.

You study microorganisms over time. How does this look in practice?

“As per the research vision of my ATTRACT project, one of the overarching goals will be to connect and compare laboratory research to field studies.

"Having spent the first 2 years of the ATTRACT project setting up the group and developing the lab work and infrastructure, we are soon moving on to field studies to see how much of what we have learned in the lab holds up under natural conditions, for example through mesocosm studies and research cruises. In light of the current Covid-19 situation, we have to wait and watch though when the field studies could be organized."

"In instances where field work is beyond the scope, we look at cells freshly isolated from their natural habitats, as against lab-grown strains.

"Often we get our cells from our collaborators or strain libraries and then study their behaviour and response. Behavioural changes are underpinned by molecular changes.

"This is where physics really meets biology. Traditionally, physicists would focus on the behavioural aspect, while biologists would focus on the molecular aspect. We try to map the two in our research, thereby approaching the problem in an exhaustive manner. On one side, we study the behaviour but also have collaborations with the LCSB where we look at the molecular level. Once we have the detail we come up with a model and test it.”

What is the goal of your research?

“Our research is fundamental in nature: We are trying to explain and develop a framework of how microorganisms adapt to changes in their environment."

"We want to understand what the key elements are which contribute to the adaptive traits in microorganisms, and how far can we keep tweaking the natural ecosystems and the natural settings before a system breaks down.

"This, in ecological parlance, is called the tipping point. Predicting tipping points using mechanistic principles can be paradigm-shifting."

"We want to put numbers on: How far can we stretch the ocean acidification? How high can the temperature of the ocean go, when is the tipping point reached? Is this the point of no return or can the system bounce back?
“Similarly, with respect to the gut, how bad a food habit can we have before the healthy microbiome in our gut gives up? Can we get a mechanistic insight into the failure of the gut?"

"Once we have the initial data, we also want to compare these seemingly unconnected systems, and look for commonalities across the systems.

“When algae are stressed, they change their metabolites in a manner that could be beneficial for generating renewable energy. There is also a strong interest now in algae as a possible source of nutrient, for example for sustenance in space.”

Your research also has relevance in Luxembourg. You study algae – the reason many of the water spots in Luxembourg are forced to close each summer. Can you elaborate?

“Every spring or summer in many places, including Luxembourg, there is a sudden and rapid growth of photosynthetic algae and cyanobacteria, commonly called algal bloom. Such blooming algae can be toxic to other aquatic organisms including fish, animals which depend on these water bodies and even humans."
Blooming algae in Luxembourg
"Despite their long history, we still do not know much about how blooms are triggered, and importantly, how can they be contained?"

“One of my postdocs is working on a project where we look at the blooming conditions from scratch - one cell at a time - and comparing the results with blooms in the oceans, rivers, and lakes. Once we get to the bottom of the mechanisms, we should be able to propose bio remediation techniques.

"Understanding blooms is one of the big open questions in marine and aquatic ecology.”

The Luxembourg research community has mobilised to tackle the COVID-19 pandemic, with dozens of research projects taking off. In this context, you have secured FNR funding for a project looking at virus-surface interactions in dynamic environments. Can you provide an overview of your project?

“The nature of the surfaces - paper, plastics, glass, or metals - and their properties (smooth v/s rough), are believed to play a critical role in determining the viability during the pre-infection phase of the SARS-CoV-2 virus.

“With the expertise in my team, we have recently taken the first steps to tease the virus-surface-environment nexus apart, to uncover how surface properties shape the stability and viability of viral particles."

"It’s intriguing why the properties of contaminated surfaces should influence the viability of virus – this is one of the fundamental questions we are trying to address in this project.

"This fundamental knowledge could equip us to innovate anti-viral solutions in a scalable and facile manner, preparing us not just against COVID-19, but also against future viral pandemics.”

With an ATTRACT Fellowship comes the opportunity for researchers to set up their own research group, for many a completely new experience. What was this experience like for you?

“I have won personal grants in the past, however the ATTRACT Fellowship is unique, since this is the first time that I got a chance to design multiple projects tied to a common thread, set up my team, and work on my long-term research vision.

"Obviously, leading a group comes with a lot of management, and with current teaching responsibilities, I have somewhat less time in the lab. Nevertheless, designing the research and setting up the group have been a fantastic experience so far! It’s great fun when you get to catch up on the results with the teammates.”

You also teach at the University of Luxembourg. What do you teach and are you able to manage it well with your other responsibilities?

“I developed a cross-disciplinary course (for Masters students and beyond) titled Physics of Living Matter. I also teach classical thermodynamics to the Bachelor students. I will also be teaching Biophysics to Bachelor students in Medicine and continuing the Physics of Living Matter course.

"I enjoy teaching a lot, this naturally helps me to find time to prepare the lectures and organize the tutorials. Besides, I think I am lucky to have team members who share my passion for teaching, so this has worked out pretty well so far.”

What part of your work do you enjoy most?

What part of your work do you enjoy most?

“I like discussing with my team – we have team meetings every week, though I enjoy the small chats and exchanges. When I first started the group, I did most of the lab training personally, but now we are reaching a point where the ‘first generation’ is taking over this part. I still sneak in once in a while!"

"It gives me great pleasure to see how much of the knowledge I transferred is being passed on, for instance, seeing my biology postdoc explain physics to a new student.”

Your science journey has taken you from India, to Germany, to the US, then Switzerland and now Luxembourg. What has this frequent moving been like for you and your family?

“International mobility was vital for well-rounded research training – I feel this in retrospect. Over the last 10 years, as I hopped from country to country, little did I know that the experience I gathered will be counted favourably towards my research profile.

"No doubt that mobility and learning under different research environments are important, though frequent change of bases might not be optimal in every case, especially for experimentalists who need time to set things up before results start to come in.

"Experimental research takes time to consolidate, so striking the right balance between mobility and research is important."

"Research stays across different continents can be helpful in developing appropriate communication styles with colleagues and collaborators. Of course, mobility could come in the way of family time and commitments, so support and encouragement from the family is a great blessing. And I had both in plenty!"

"I am happy that the ATTRACT Fellowship has now given me the stability, and the time to consolidate my research in Luxembourg."

"I do not have immediate plans for research stays elsewhere, however at some point in future, I might like to explore opportunities using FNR’s INTER Mobility grants.”

Discover more about Anupam Sengupta's research in the video below.

Anupam Sengupta's journey to ATTRACT

1983: Born (India)

2003 – 2008: BS in Mechanical Engineering and MS in Thermal and Fluids Engineering (Indian Institute of Technology, Bombay, India)

2008 - 2009: Application Engineer working on thin film instabilities and gas entrapment in meso-scale coating and drying processes (Fluid Measurements and Projects Technology GmbH, Germany)

2009 - 2012: PhD in experimental Soft Matter Physics (Max Planck Institute for Dynamics and Self Organization, Germany)

2013 - 2014: Max Planck Institute Postdoctoral Fellow in micro-scale dynamics of liquid crystal flows (Max Planck Institute for Dynamics and Self Organization, Germany)

2014 - 2017: Cross-Disciplinary Fellow, Human Frontier Science Program. Studied the biophysics of microbial nutrient uptake in flow at the Massachusetts Institute of Technology (MIT), USA (2014-15), and ETH Zurich, Switzerland (2015-17)

2017/18: Secures 1.5 MEUR FNR ATTRACT Starting Grant (over 5 years) and relocates to Luxembourg to establish the Sengupta Lab at the University of Luxembourg

ABOUT ATTRACT

The FNR ATTRACT programme offers promising young researchers the chance to come to Luxembourg to set up their own research group.

The financial contribution by the FNR can be up to 1.5 MEUR for Starting Investigators (Postdoc & Junior Researcher level) or 2 MEUR for Consolidating Investigators (Established Researcher level). ATTRACT has one Call for projects per year, which applicants must coordinate with the proposed host institution.

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