Dr. Vidhya Rangaraju
Group Leader Max Planck Florida Institute for Neuroscience
Postdoc fellow Max Planck Institute for Brain Research
PhD Weill Cornell Medicine
Life, as we know it, depends entirely on energy. Every breath, every muscle twitch, and the production of even the tiniest protein rely on our bodies’ remarkable ability to transform organic matter into energy. This delicate balance between metabolic supply and demand is particularly crucial in the brain, which accounts for around 20% of our overall energy consumption. Dr. Vidhya Rangaraju is fascinated by how neurons and synapses meet their extensive and ever-changing energy demands. Now a Research Group Leader at the Max Planck Florida Institute for Neuroscience, Vidhya and her lab seek to unravel the cellular and molecular mechanisms underpinning energy supply in the brain.
Vidhya’s journey into neuroscience was somewhat circuitous. She began her academic career as an undergraduate in Industrial Biotechnology at Anna University in Chennai, India, a degree that combined elements of chemical engineering and molecular biology with a focus on industrial applications. In her senior year, she noticed many of her peers applying for PhD programs. Although Vidhya enjoyed the biological engineering components of her coursework and was interested in research, she was also mindful that embarking on a PhD was a significant commitment. Keen to test the research waters a little more before diving in, she spent a year as a Research Assistant at the National Centre for Biological Science in Bangalore. There, she contributed to developing molecular tools for measuring intracellular pH. This experience not only helped her expand her technical skill set but also sparked a newfound amazement at how novel experimental tools can unlock exciting biological questions, solidifying her desire to pursue a PhD.
Vidhya undertook her PhD in the lab of Dr. Timothy Ryan, a neuroscientist based at Weill Cornell Medicine of Cornell University in New York City. Despite her limited experience in neuroscience, she found Tim’s lab to be an ideal fit, perfectly aligning with her interest in developing tools and using analytical skills to study molecular and cellular processes. Her PhD work focused on developing a reporter to measure ATP— the primary energy currency in cells— in synaptic terminals to investigate energy dynamics during synaptic transmission. “Synapses are hot spots of energy consumption,” Vidhya explains. Many key synaptic processes—calcium signaling, ion movement, and vesicle release—are highly energy-intensive. While synaptic transmission had been studied for decades, very little was known about how synapses generate the energy necessary to support these processes. Vidhya’s work centered on using luciferase, an enzyme that emits photons in the presence of ATP, as an ATP sensor. No one in Tim’s lab had used this reporter before, and it was up to Vidhya to get it working. After a year of optimizing and many hours spent in a pitch-black microscope room listening to Beyoncé and Taylor Swift, she successfully imaged ATP signals from synaptic terminals. Vidhya remembers feeling elated: “It was fascinating to see the tiny dots of energy within synapses for the first time. From then on, I knew it was going to be an exciting ride!” Having established an effective means of measuring synaptic ATP, Vidhya concluded her PhD by demonstrating that synapses synthesize ATP on demand to supply the energy required for synaptic transmission.
With this exciting new insight into synaptic energy dynamics under her belt, Vidhya knew she wanted to pursue a postdoc. After attending a talk by Dr. Erin Schuman, a Principal Investigator and Director at the Max Planck Institute for Brain Research in Frankfurt, Vidhya arranged a meeting with Erin and was soon invited to visit her lab in Germany. Despite the daunting prospect of moving to a new country yet again, Vidhya felt a strong connection with the lab during her visit and accepted a position there. The Schuman Lab studies the mechanisms underlying synaptic plasticity and protein synthesis in neurons. During her postdoc, Vidhya focused on investigating the role of neuronal mitochondria in these processes. Mitochondria are membrane-bound organelles in the cell’s cytoplasm that generate significant quantities of ATP to support intracellular processes. Vidhya was particularly fascinated by the differences between axonal and dendritic mitochondria. While axonal mitochondria are small and mobile, dendritic mitochondria are much larger and generally fixed in place due to their interactions with the cytoskeleton. Vidhya was keen to investigate the understudied role of dendritic mitochondria in synaptic function. She discovered that disrupting dendritic mitochondria while stimulating individual synapses abolished both synaptic plasticity and stimulus-driven protein synthesis, but only when the disrupted mitochondria were in close proximity to the stimulated synapses. This finding indicated that dendritic mitochondria act as spatially confined energy sources, crucial for supporting local protein synthesis and synaptic plasticity.
As Vidhya neared the end of her time in the Schuman Lab and began applying for faculty positions, she felt anxious about transitioning from postdoctoral scientist to group leader. In a candid conversation with her supervisor, she admitted her fear of failing and disappointing those who believed in her. Erin offered a valuable piece of advice: "It’s okay to fail!". This simple reassurance made Vidhya realize that she had been creating a mental barrier by focusing on everything that could go wrong. By giving herself the freedom to fail, she felt empowered to take the leap and successfully secured a faculty position at the Max Planck Florida Institute for Neuroscience. However, shortly after she arrived to set up her lab, the COVID-19 pandemic struck. Among the many challenges of the pandemic was the lack of opportunities to build relationships with other scientists. "It was just me and my lab members," she recalls. Facing an extended period of scientific isolation, one of her mentors advised her to proactively reach out to others for structured mentorship and guidance. This advice completely transformed Vidhya’s perspective. She made a concerted effort to connect with and build structured mentor-mentee relationships with other scientists and pursue collaborations within her institute and beyond. As a result, she now has a network of mentors and peers whom she regularly consults for advice on grants, figures, and more. This experience not only highlighted the importance of good mentorship and support but also helped Vidhya realize that it is possible to be a successful, independent scientist while still benefiting from the community around her. “Just because you are independent doesn’t mean you have to do it alone!” Vidhya says.
The Rangaraju lab has now been up and running for four years, and Vidhya is excited to see what the future holds for her and her group. A key focus of the lab, building on Vidhya’s PhD and postdoctoral research, is to uncover the cellular and molecular mechanisms that underpin mitochondrial function in neurons, with a particular emphasis on their role in neurodegenerative diseases. Her team has already identified a protein called VAP, which functions as intracellular ‘glue’ that keeps mitochondria fixed in place by anchoring them to the cytoskeleton. Notably, mutations in VAP, especially the VAPB paralog, have been linked to the motor neuron disease ALS, perhaps alluding to a role for mitochondrial dysfunction in the pathology of this disease. Vidhya’s group uses in vitro and in vivo approaches to examine the relationship between VAP, mitochondrial activity, and neuronal function in healthy and diseased states. With so many exciting projects on the horizon, alongside balancing the various demands of being a group leader, mentor, and parent, Vidhya is clearly an expert at knowing exactly where to channel her energy.
Find out more about Vidhya and her lab’s research here.
Listen to Nancy’s full interview with Vidhya on May 29, 2024 below!
