Professor Purusharth I. Rajyaguru

Written by Dr. Anca F. Savulescu

Dr. Purusharth I. Rajyaguru is an Associate Professor in the Department of Biochemistry, at the Indian Institute of Science (IISc), in Bangalore, India. He was a DBT-Wellcome India Alliance Intermediate fellow from 2013 through 2019. Dr. Rajyaguru received his PhD from the Centre for Cellular and Molecular Biology (CCMB) at Hyderabad (India), where he studied the degradosome, an RNA degradation complex, under the supervision of Prof. Malay Kumar Ray. He considers himself fortunate for the opportunity to undertake his PhD training at CCMB, a premier research institute in India. Furthermore, according to Dr. Rajyaguru, “My exposure to experimental biology before starting my PhD was extremely limited. Therefore, learning to do experiments and learning to live with the inevitable failures took quite a bit of getting used to. CCMB provided a wonderful environment to inculcate the desire to do research in me.” Dr. Rajyaguru added that his PhD mentor Prof. Ray always amazed him with the extent of his knowledge outside RNA biology: “It was inspiring how he managed to read as much as he did and be academically aware of the latest exciting research. Besides, he gave me the space and freedom to decide the pace of my work.”

Following his PhD studies, Dr. Rajyaguru travelled to the US and joined the lab of Prof. Roy Parker at the University of Arizona for his postdoctoral studies. In Prof. Parker’s group, he studied regulation of eukaryotic mRNA translation and decay. Dr. Rajyaguru says that Roy Parker has been a key role model for him: “The first year of my postdoc in Prof. Parker’s lab was a steep learning curve. He always impressed upon lab members to think about ‘why’ a certain biological question was important to answer. While working on a grant proposal, Prof. Parker often involved the entire lab into discussions to understand what most of us were excited about as a group. This was a great learning experience for me.” When he moved to the US, Dr. Rajyaguru quickly realized the differences between doing research in the US as compared to India. Most of these differences stemmed from the better availability of funds and more complete research infrastructure that had been established in the US. Dr. Rajyaguru explained “My stay in the US as a postdoc was instrumental in me realizing that I liked academia and could actually make a career in academia. I always wanted to come back to India to be close to my family. Towards the end of my postdoc (in late 2012 and early 2013) due to the financial downturn in the US, it was evident to me that sustaining a research group in India was likely more probable than in the US at that time.” He reasoned that although the quantum of an average research grant was much smaller in India (when compared to the US), the probability of getting a piece of that smaller pie was much higher. Dr. Rajyaguru said, “It was both unfortunate and sobering to witness many deserving PIs close their labs in the US and leave academia due to lack of funds at that time.”

At IISc, Dr. Rajyaguru’s group aspires to unravel mechanisms underlying mRNA fate decisions mediated by RNA-binding proteins with low complexity sequences. mRNA fate decisions are critical for various cellular processes, as well as playing roles in diseases, such as cancer and neurodegenerative disorders. Specific projects in his lab focus on (1) understanding the mechanisms underlying RNA granule disassembly, (2) characterizing the crosstalk between RNA processes in the nucleus and cytoplasm, and (3) understanding the dynamics of arginine methylation. Dr. Rajyaguru is excited about all of these projects, and he believes that a wonderful aspect of being a PI in academia is that one can execute many of the ideas that excite him/her. He added, “We have (and will continue to) ask fundamental questions in our laboratory pertaining to mRNA fate decisions. The possibility that one such fundamental question pertaining to how RNP condensates disassemble could possibly lead to therapeutic intervention is exhilarating. This is based on our recent observation that RGG-motif containing peptides disassemble RNP condensates such as P-bodies and disease relevant aggregates of EWSR1 observed in Amyotrophic lateral sclerosis.”

“Interactions with people [outside our field] have enabled me to grow and evolve as a scientist. I would highly recommend early-career researchers to engage in such activities. Although these take up a lot of time away from doing research, they can play a critical role in the growth of the researcher. Besides, I enjoy reading new literature and these activities provide me with ample opportunity to do that!”

In addition to his research, Dr. Rajyaguru places an emphasis on teaching and serving the scientific community. At IISc, he engages in teaching undergraduate and graduate students which he finds highly rewarding. He is an Associate Editor at WIRES RNA and BBA Advances. These editorial activities have allowed Dr. Rajyaguru to network with several scientists within and outside his specific field. “Interactions with these people have enabled me to grow and evolve as a scientist. I would highly recommend early-career researchers to engage in such activities. Although these take up a lot of time away from doing research, they can play a critical role in the growth of the researcher. Besides, I enjoy reading new literature and these activities provide me with ample opportunity to do that!”, he said. Dr. Rajyaguru also served as part of the RNA Society’s journal publication committee between the years of 2020 and 2022. He stated, “This effort was initiated by Prof. Eric Wagner during the pandemic and consisted of a diverse group of volunteers ranging from postdoctoral fellows to senior PIs (and everyone in between). The aim was to help the journal gain better visibility by highlighting the high quality science published in RNA.” Dr. Rajyaguru was introduced to the RNA journal early during his PhD. He added: “When I started as a PhD student, the review article titled, ‘Emerging features of mRNA decay in bacteria’ by Deborah Steege served as an excellent guiding light for me to learn about bacterial mRNA decay.”

Dr. Rajyaguru’s path in his scientific career has not always been smooth. According to him, managing and mentoring lab members with different kinds of personalities and motivation levels was a major challenge when he first started his independent group at IISc Bangalore. Dr. Rajyaguru adds: “The realization that every research trainee is different and therefore requires a different mentoring approach took some time and adjustment for me. I made some mistakes along the way, but I have become wiser from those experiences. It would not be wrong to admit that I am still learning this aspect of being a PI.” Dr. Rajyaguru also mentioned that asking good questions will likely lead to good answers. He adds: “Of course the definition of a ‘good’ question can be subjective and influenced by the training the researcher has undergone. But spending sufficient time on formulating the research question/problem often helps to identify the questions that I do not want to spend my time and resources on.” He therefore encourages his group members to identify several questions at the beginning of their tenure and then pick the “best” question of the lot to address. According to Dr. Rajyaguru: “Once a question/problem has been identified, patience and persistence are the keys to making scientific breakthroughs.”

Dr. Rajyaguru has been a regular attendee of the RNA Society’s Annual meeting and he states that the scope of interactions provided by this meeting to the RNA community is unparalleled. He remembers a specific incidence that occurred during the RNA Society’s 2017 meeting in Prague, “I was going through the posters and noticed another researcher with a name tag that was the same as someone who had shared a construct with me during my postdoc. I introduced myself to him and also thanked him for sharing the plasmid construct. It turned out that this researcher was not whom I assumed him to be, even though they shared the same name! We laughed about it and discussed our mutual interests. Upon returning from the meeting, we continued our discussions over emails and zoom meetings about our research plans and possible collaboration. I am excited that we have indeed initiated a collaboration and my student visited his laboratory to perform the initial experiments. Based on this data we submitted a grant together and are eagerly awaiting its outcome. I am happy that I introduced myself to this individual at the Prague meeting which resulted in this collaboration.”

Lastly, Dr. Rajyaguru is very excited about RNA molecules that form G-quadruplex structures. Furthermore, in his lab, they focus on RNA-binding proteins with RGG-motifs that bind RNA G-quadruplexes. You can follow Dr. Rajyaguru on Twitter – @rajgodhuli (personal) and @Labrajyaguru (lab). To learn more about his group and their work, you can visit his group’s website.