Fundamental Research can be stranger than fiction ! Just imagine accelerating particles (electrons) to the speed of light to create a highly intense X-Ray light source that can potentially take high-resolution and high-contrast images of nanoscale objects.

Ramakrishna Vasireddi, our next pathbreaker, Particle Physicist at the Synchrotron facility SOEIL, works on cutting-edge microfluidic techniques that combine ultrabright X-rays (XFELs and Synchrotrons) to make “molecular movies” of structural matter with atomic resolution at ultrashort time scales to investigate dynamic processes in action.

Ramakrishna tells Shyam Krishnamurthy  from The Interview Portal about his exposure to Microfluidics that drove his curiosity to explore the area further as a postdoctoral Researcher at Synchrotron SOLEIL

For students, pure science gives you powerful tools to witness nature in ways that very few can!

Ramakrishna, tell us about your background?

I grew up in a small village named Pinapenki near Bobbili city in Andhra Pradesh. My parents were farmers from a simple and lower middle-class family. Growing up in a farming community and helping my parents in farming has instilled values of hard work within me. I learned a lot from my parents, especially how working hard helps people stay aloft despite all hardships. Being from a remote village, I never wanted my parents to spend money on my education and always hoped to be a meritorious student. This determination spurred me to work hard and gain admission into elite institutes throughout my studies. Today, my life is a lot more different from what it was when i grew up. I achieved the financial success through a combination of hard work and dedication. I completed my schooling from Zilla Parishad High School (ZPHS), and this is when I gained the opportunity to participate in a few science exhibitions and motivated myself towards basic science. During my masters’ studies, Prof. N. Veeraiah inspired me a lot towards a career in research. His motivational speech and teaching has always motivated me to pursue a research career in prestigious institutes. My passion for academic success didn’t stop me from pursuing extra-curricular activities; I was actively involved in sports, and played badminton and cricket at district and zonal level during school and college days.     

What did you do for graduation/post-graduation?

I am currently working as a postdoctoral Research Scientist at Synchrotron SOLEIL, PROXIMA-1(Macromolecular Crystallography, Dr. Leonard Chavas) beamline in Paris, France. I received my Doctorate in Physics in the area of Microfluidics and X-Ray Scattering from the Hamburg Centre for Ultrafast Imaging (CUI), Department of Physics, University of Hamburg at Deutsches Elektronen-Synchrotron (DESY), Germany. I studied masters in Physics with a specialization in Condensed Matter Physics. My bachelors (Physics, Chemistry, and Mathematics), intermediate and schooling were from Bobbili, Andhra Pradesh.

What made you choose such an offbeat, unconventional and fascinating career?

I was fascinated with my bio-science teacher at school as his focused teaching skills, domain knowledge and motivation had greatly influenced me to head towards a science-oriented career. During my graduation, there was a significant push towards research. It was Prof. N. Veeraiah, the man behind the scenes who motivated me to pursue further studies and guided me about various entrance exams like GATE and CSIR-NET. His guidance and motivation helped me pursue higher education. During my masters, I was attracted towards condensed matter physics and nano-bio science research by eminent researchers across academia and industries. The biggest turning point in my career came after joining India’s premier institute, the Indian Institute of Science (IISc), as a project associate. At IISc- Bangalore, I had a chance to learn bio-science (Prof. Bikramjit Basu) and microfluidic device fabrication techniques. During this time, I published a few high impact international journals, an Indian patent and attended few international conference proceedings. We designed and fabricated a microfluidic device for biological sample preparation along with selective and high throughput screening of relevant biomolecules, such as nucleic acids and proteins. The integrated device had a sequence of individual steps such as microfluidic mixing, nanostructure assisted enhanced electrical lysis, thermal denaturation of double-strand DNA molecules, binding-wash-photo-cleavage and detection of clean DNA. The primary aim of the proposed device was to extract, screen and detect from clean dsDNA molecules, which would be further used in detection of the degree of infection. Such experiments require complex design and fabrication processes, as well as choice of bio-nano materials, loading infected samples and understanding each step, which was were very challenging. Working with experts within a team, we finally developed an integrated device for biomolecule detection using a lot of optimization parameters and experts within the teamwork. The developed technique has broad applications from disease detection to next-generation gene sequencing, on-chip synthetic biology. 

The scientific knowledge i accrued inspired me to start looking for Ph.D. opportunities in the field of physics and nano-bio science. I managed to get around 3 Ph.D. offers (one Marie Curie fellowship) from all over the world. I finally chose to go to the University of Hamburg’s Cluster of Excellence CUI to work with Prof. Martin Trebbin at the one of the world’s prestigious particle accelerator institutes DESY. This opportunity was a big leap for me, to be a part of one of the fastest-growing technologies where I could exhaustively leverage my skills in X-Ray science and microfluidic devices. The interaction of X-rays with matter offers possibilities to study its structure down to the atomic scale. Ultrafast structural dynamic processes, like proteins, nanoparticle growth and aggregation, are starting to attract a lot of attention nowadays. TEM or SEM imaging cannot be used for the time-resolved investigation of such processes due to time-consuming sample preparation. Since the last years, real-time in situ X-ray experiments have become popular, as modern X-ray sources, mostly synchrotrons, can provide highly intense and brilliant polarized X-ray beams. I learned a lot from Prof. Martin Trebbin. Besides his guidance, he gave me the freedom to work in different areas of research, which helped me deepen my knowledge on ultrafast structural determination of liquids to study structural dynamics of proteins and the nucleation and growth of nanoparticles. A fundamental understanding of these fascinating processes and techniques will allow us to control them systematically and impact the world. 

Currently, my research focuses on In-vivo crystallography and single-particle/cell imaging using modern structural determination techniques in combination with state-of-the-art microfluidics.

How did you plan the steps to get into the career you wanted? Or how did you make a transition to a new career? Tell us about your career path

Since I came from a lower middle-class farmer family, I had no guidance towards higher education and research. So my career in the research field started after many failures. There were no training institutes, nor many people among my friends and relatives who had higher education and a career in research. Luckily, during my masters, Prof. N. Veeraiah pushed me towards research. His teaching skills and motivation inspired me to do my doctorate. The real turning point in my career came when I started a Ph.D. from the University of Hamburg, Germany (DESY, CUI Funding). This opportunity gave me a big career break to be a part of one of the fastest-growing research institutes where I have exhaustively leveraged my skills in microfluidic device technology and condensed matter physics. One of the privileges I have had during my Ph.D. was the freedom given by my supervisor (Prof. Martin Trebbin) in exploring and working with a variety of techniques. My research involves making “molecular movies” of structural matter with atomic resolution and at ultrashort time scales (Femto to attoseconds). I work on cutting-edge microfluidic techniques to combine ultrabright X-rays (XFELs and Synchrotrons) to understand these fast dynamic processes in action. A major part of my research activity aims to translate my fundamental understanding into integrated systems involving imaging, resolution, sensitivity, structure-function relationship and interfacial properties.

I had married my wife Revathi during my final year of my doctoral studies. I’m fortunate to have such an intellectual and understanding wife like her in my life. She has always been supportive of my dreams to be a research scientist. I would like to add that I am grateful to my family and friends who have stood beside me at all times. Last but not least, I would like to mention my family friends, Dr. Brahmanandam, Mr. Srinu and Mr. Kasi Naidu for their continues support at every stage of my career.

How did you get your first break?

As mentioned earlier, my first leap was when I got selected for Ph.D. at the German Center for Excellence CUI, University of Hamburg at DESY, Germany. During my days at the Indian Institute of Science (IISc), I was selected for two fellowships at the same time. One from the German Center for Excellence CUI and the work was connected to microfluidic to combine X-Rays to understand time-resolved structural dynamics. And the second one was a Marie Curie fellowship from KU Leuven, Belgium and the work was connected to recycling materials and reuse. I had selected the first option, as it was a growing area and related to my previous research experience on microfluidic device technology for biomolecule detection and screening (patented) and diagnostic applications. During my Ph.D., I was lucky to supervise masters’ and bachelors’ students from the University of Hamburg and other elite European Universities. This provided me the experience in mentoring and supervising younger research talents from diverse backgrounds.

What were the challenges? How did you address them?

As I came from a lower middle-class farmer family, my life was full of challenges to balance my studies and financial issues. The main challenge was to enter a government school and university through a merit list for higher education. My hard work and sacrifice of staying away from home paid off well and led to a fruitful Master’s degree. I’m fortunate to have supportive and caring parents (Chinnammi & Satyam Naidu) and an elder brother (Maheshewara Rao). During my research at IISc Bangalore, I started applying for Ph.D. positions abroad. It was a tough start, and I didn’t get any place initially. Though it was very painful, I never thought of discontinuing my interests. During this time, I spent sleepless nights, tried to read a lot and kept searching for opportunities. In the meantime, I published a few papers in international journals. Ultimately everything turned out well and I got two offers at a time and I chose the opportunity from Germany.

The next challenge was ultrafast structural determination techniques using X-Rays through X-ray free-electron lasers and synchrotrons. Visualizing the structural dynamics of matter with atomic resolution and at short time scales (Femto- to attoseconds) is of great interest in many areas of physics, materials science, biology and chemistry. For understanding these superfast dynamic processes (ultrafast phenomena), one requires the combination of advanced analysis techniques such as the X-ray scattering and spectroscopy. Understanding fundamental science is not so difficult if you do real experiments. This simple fact makes modern science so exciting and challenging, but understanding these techniques is not easy. Being from a general Physics background, I had little knowledge in X-Ray physics. My Professor (Dr. Martin Trebbin) and my colleagues in Trebbin-lab helped me a lot in enriching my skill sets and adapting to this new field.  

Where do you work now? 

Currently, I am working as a Postdoctoral Research Scientist at Synchrotron SOLEIL in Paris, France. My current research focuses on the development of X-ray compatible microfluidic devices for time-resolved structural dynamics of bio-macromolecules and single-cell imaging. Mainly, I am involved in the ANR project (French funding), with the aim to develop X-Ray compatible microfluidic devices for crystal trapping, sorting, and presentation to the X-Ray beam for very high throughput in-vivo serial crystallography experiments. The developed X-Ray compatible microfluidic device technology will help the scientific community, and developing those technologies at a user servicing society like SOLEIL is of major research interest. I’m also involved in another ANR project, which is aimed at developing GDVN based microfluidic spray devices for the preparation of time-resolved cryo-EM biological samples. These research projects will help me understand structural biology in greater depth and move my research towards bioscience.

How does your work benefit the society? 

My research interests and activities are focused on time-resolved structural dynamics of proteins, nucleation and growth process of nanomaterials by combining state-of-the-art microfluidic techniques with X-rays from modern free-electron lasers (XFELs) and synchrotrons. A major part of research activity aims at translating a fundamental understanding into integrated systems involving imaging, resolution, sensitivity, structure-function relationship and interfacial properties. 

I feel that the opportunities at the University of Hamburg at DESY and Synchrotron SOLEIL are major career leaps which provided me with excellent professional growth. My research not only provides a fundamental understanding of superfast dynamic processes in action but also addresses the lack of working knowledge in real-life systems such as understanding the structure of new viruses like novel Coronavirus (COVID 19). Also, it helps different research groups worldwide in potentially applying this technology to different scientific communities, i.e., structural biology, material science, chemistry, etc.

Tell us an example of a specific memorable work you did that is very close to you!

There are several exciting moments in this research field, such as journal publications, patents, and writing grant proposals, as well as public interaction programs like science festivals and science quest, etc. When I was in IISc, I worked on a patent which was related to medical devices for the detection of biomolecules. That was a challenging project and my career, to some extent, followed that work. Another, I worked on novel (X-ray compatible) microfluidic sample environments that address specific experimental conditions for X-ray applications and oxygen-sensitive proteins. In particular, these devices that allow crystals are loaded and trapped at known positions, ready for very high throughput in-vivo crystallography experiments using synchrotrons. The key aspect of this system is an alternative way to obtain crystals of proteins for which classical in vitro crystal growth remained unsuccessful, as well as the opportunity to study functionally important post-translational modifications. This device sample environment is not just limited to X-ray experiments but will also be very useful for time-resolved solution-phase UV/VIS/IR spectroscopy studies and potentially for drug delivery applications. Fabricating such kinds of X-ray compatible devices at lower resolution (below 10 micron) is a very challenging task. Still, due to my previous device experience on different materials and techniques, finally, I achieved it. I am very happy to develop such kind of device technology, as these devices will help the scientific community and those utilizing these technologies at a user servicing society like synchrotron SOLEIL where it is of major interest.

Your advice to students based on your experience?

I come from a very modest family background and small village. However, one thing that kept me motivated and pushed me to do something good was the freedom that my parents gave me to choose my career path. I have faced many problems at all stages of my life, but I never turned back. In my experience, hard work, determination and honesty are the qualities that are required to be successful in life. “Nothing in this world is impossible,” and anything can be done by self-confidence, positive outlook and hard work. It’s always nice to feel amazing when you know that you’ve done something that makes your parents so proud of you. Enjoy your journey rather than the result. Finally, I believe “Understanding of fundamental science is not so difficult if you do real experiments.”

Future Plans?

I am still in the early stage of my career as a researcher. At this stage, I need to get some experience in the mentoring and supervision of younger research talents.  Also, I would like to share knowledge and build strong collaborative links with different research groups and write grant proposals to establish my research laboratory as my dream.  My future plan is to get a faculty position in India, then to develop my research labs in the area of BioPhysics and encourage younger research talents.