What's your earliest recollection of the time when you realised what your calling was? For Dr Manjula Mummadisetti it was way back in school while building science models of erupting volcanoes and a device that effectively repels mosquitoes. That's when she had a vague epiphany that only grew stronger over the years. The now 35-year-old has always let science hand-hold her through her academic decisions. That's how she ended up working on corals for her post doctorate research. Actually, it was famous American oceanographer Dr Paul Falkowski at Rutgers University who implored her to apply her love for studying proteins to corals. It wasn't exactly what Manju had in mind but she was game. And boy, how this changed the tides.
This researcher's study was published in the Journal of the Royal Society Interface in April 2021, news that truly delighted her. All those hours of analysing data paid off. Manju's research suggests that corals, indeed, can withstand climatic changes. We ask the researcher, who has spent seven years of her life in the city of Hyderabad, all about her fascination for proteins, what human bones have in common with corals and a lot more. Excerpts from a detailed and insightful conversation:
Picking research after a master's degree is still something that's seen as unconventional. Do tell us how you chose this path.
I was highly attracted to Science as a high schooler. I enjoyed working on Science projects back then. I remember making projects such as a volcano that erupted as an effect of a chemical reaction, showcasing a model of Tokyo city that utilised the concepts of reflection of light, and even a mosquito repellent device that produced a certain sound frequency to repel mosquitos. Hence, I was confident that I would enjoy learning Science after my class X as well. I continued to choose Life Sciences after my Class XII and pursued my BSc in Microbiology, Botany and Chemistry.
I was good at Chemistry which led me to take part in a National Chemistry Quiz in which my team won first place. I was fascinated by the chemistry that our biological systems utilise to perform functions. This led me to pursue Biochemistry for my Master’s. The Biochemistry department at Osmania University was a game-changer for me. I had great teachers who made an impact and instilled a scientific curiosity in me. I wanted to continue my quest for knowledge and pursue research in the future. I also wanted to support my family financially hence, I started working part-time at GE Finance during my undergrad and MSc. I was doing really well in the organisation and it gave me a feeling of independence, but I always knew that I would pursue a long-term career in Science.
This is when I decided to get a PhD so I started looking for universities and shortlisted a few. I contacted the professors from the research labs of my interest to understand their work and finally, decided to pursue my PhD from the Louisiana State University.
And how did you come to pick the area of protein? Surely the seeds must have been sowed much before.
I was always fascinated with proteins, especially when I learnt that proteins are the workhorses of life and that they perform all the functions in a cell, during my undergrad. The three-dimensional structures of these proteins always fascinated me. The fully-folded 3D structure of a protein helps it interact with other proteins that perform specific functions. If these proteins do not fold in the correct 3D structure (protein misfolding), it can cause diseases like Alzheimer’s, Parkinson’s and other neurodegenerative diseases.
During my PhD, I worked on an amazing protein complex (an assemblage of more than 20 proteins that work as a unit) called Photosystem II. I remember studying in Class III that plants take water and light and provide us oxygen. Not until Class XII did I learn the name of the protein complex that releases oxygen from the leaves. And during my PhD, I worked on this Photosystem II complex that’s responsible for life on this planet. Solving the three-dimensional structures of these Photosystem II proteins and understanding their interactions within a complex unit with other proteins was an enriching experience.
I learnt to think of a scientific problem in a multidimensional manner. My PhD journey wasn’t easy but I can say that getting a PhD was my best decision. I enjoyed conversations with my PhD advisor who loved sharing his knowledge. I would spend hours together with my friends and lab members talking about interesting scientific topics. The learning curve during my PhD was quite steep. To gather knowledge, I had to collaborate with other PhD students to initiate a journal club (that did not exist for Plant Sciences in my university at that time). As part of the club activity, we discussed current scientific published papers on plant biochemistry that helped all the members in their field of research.
I had to face quite a number of challenges during my PhD journey. The projects I initiated during the first two years went in vain since another research group published their results on the same problem before me. I had to gather myself and re-initiate new projects to ensure my graduation wasn’t delayed. Working late nights and staying focused at times was difficult, it took a physical and mental toll. However, I had great support from my advisor, family members and friends. The hard work has finally paid off in the form of earning a PhD degree as well as publishing research in high-impact journals.
You had mentioned that you were implored to look beyond your field and apply what you had learnt to corals at Rutgers University. Do regale us with that fascinating tale.
My PhD in Biochemistry in the field of photosynthesis got me interested in working with Dr Paul Falkowski. His lab works on different aspects of photosynthesis, corals (since corals have small photosynthetic organisms as their symbionts), biogeochemistry, oceanography, biophysics, protein design (designing new protein molecules with novel activity, behaviour or purpose) and so on, is notable. I interviewed for a photosynthesis-related protein chemistry role, however, during the process, we explored the possibilities of applying protein chemistry on corals and work on coral biomineralisation, a field with more unknowns where the tools to perform reverse genetics or molecular biology aren’t developed yet.
So, I finally worked on stony corals (the reef-building corals), Stylophora pistillata, during my postdoc. It took almost a year to design/redesign and optimise/re-optimise the experimental conditions and another year to perform all the experiments to finally get some significant results, followed by several months of sorting through large amounts of proteomics data which led to the conclusions of the research. The data was highly appreciated during one of the international conferences by several scientists and this work was recently published in the Journal of the Royal Society Interface.
Do tell us, in layman's terms, the project you were associated with and how it challenged you in new and unique ways.
The project I was working on is called biomineralisation, that is, the process of formation of minerals (biologically) in the stony corals. Let me start by giving a little background:
Coral reefs are extraordinary ecosystems, providing habitat for many species of marine organisms and hence, are sometimes called the 'rainforests of the seas'. Stony corals evolved over the past 400 million years and over geological time, formed massive reefs in shallow subtropical and tropical seas. Predicting the survival of stony corals based on their adaptability to global climate change through millions of years requires an understanding of, among other things, their mechanisms of biomineralisation (the reef-building process by secretion of calcium carbonate).
Stony corals are simple animals made of four cell layers. Their life cycle transitions from a planktonic non-calcifying organism that settles on a hard substrate, followed by metamorphosis to form a polyp with a mouth to capture food (zooplankton) and, for many coral species, later budding into many polyps to form colonies. The stony corals remain at their site of attachment for the rest of their lives and deposit an external biomineral material made of calcium carbonate called skeletons. The coral colonies can grow on a large area on top of the secreted skeletons from former colonies and hence, eventually forming a large reef.
The formation of these skeletons is a tightly controlled biological process, where the animal secretes and deposits an organic matrix of biomolecules that are arranged in the skeleton in a highly organised fashion. At a nanoscale, these biomolecules control the biomineral deposition process, shape, size and three-dimensional organisation, as well as the mechanical properties and plasticity of the biomineral material. In this study, recently published in the Journal of the Royal Society Interface, we show that several proteins are required to work together to create the optimal conditions for biomineralisation to occur and these proteins are not located randomly, but are spatially highly-organised. This work provides information on the spatial patterning of the calcification space as a new mineral is formed between the living tissue of the animal and the substrate or the older skeleton. We present a high-level spatial interaction network of the skeletal proteins, which can likely be generalised to all stony corals, which is incredibly important to understand the mechanisms of coral biomineralisation and these important animals’ persistence as we all live through the era of anthropogenic climate change.
It's absolutely mind-blogging to know that our bones and corals are both made of proteins, well at least to a certain extent anyway. Do describe how you established this connection.
Humans are also biomineralisers. We form bones, teeth and otoconia, the calcium carbonate crystals (in the saccule and utricle) of the ear. Otoconia or ear bio-crystals sense the linear acceleration and gravity to assist with body balance. Coral reefs or skeletons are similar to bones as they both contain proteins and other biomolecules. These proteins are very special as they have the ability to form calcium carbonate or calcium phosphate in corals, and humans respectively, in a buffered environment or even on a Petri dish in the lab. I used the technology of protein sequencing (proteomics) to identify the proteins in the coral skeleton and compared them to the proteins in bones. There are some striking similarities functionally as well as at the sequence level among an acid-rich protein in both of these organisms.
It all concluded with the paper, of course, where you proved that corals organise proteins to form rock-hard skeletons. How was it to distill all your work into that paper?
Quite frankly, it wasn’t an easy task. The idea is quite novel, however, none of us knew that it would lead to anything significant. It required trying several strategies and, of course, inputs and hard work of undergraduates and research associates in the lab, to grind several grams of coral skeletal powder into extremely fine 60-micrometer size, constantly cleaning and extracting protein free of chemicals and contaminants — an extremely strenuous process, followed by a very lengthy process preparing samples ready for analysis. I spent weeks sitting in front of the computer either working and sorting crystals on scanning electron microscopy or looking at the proteomics data and analysing it.
Proteomic Data analysis also required coming up with new ways to analyse and make sense of the data, which meant months of sleepless nights to make sense from it, several months of writing and communicating with the other authors of the paper and getting the opinion of other scientists in the field before it was finally published.
Tell us the exact difference your research is capable of making not only in bringing us closer to understanding these beautiful organisms, but also saving them.
Well, this research emphasises the ability of these organisms to withstand climatic changes. Basic research on the coral structures and coral skeletal structures at their nano-scale level are highly important to understand these organisms and their resilience to high stresses. This research from a scientific perspective shows the topology of the coral skeleton, a field view of how different proteins are arranged in the skeleton and how the unified action is necessary to form these robust massive structures.
Now you are treading a new different path, Senior Scientist at AVMBioMed. How is it going and what does the future hold?
The beautiful world of proteins has always fascinated me. In my current role, I continue to work on them. I use new technologies in the field of proteomics to analyse several proteins at once. This is a level up in complexity from my previous work on proteins as I study the modifications that occur on proteins (as a part of normal cellular response or a protein modification that’s generated in response to certain environmental stresses or other pathogenesis/disease conditions). I now hope to apply the gained skills and contribute towards the early biomarker discovery in different diseases including cancer.
For more you can reach out to her at linkedin.com/in/manjula-mummadisetti
