Rangaraju Lab

We study Neuroenergetics

Vidhya Rangaraju

Research Group Leader

(561) 972-9414

Vidhya.Rangaraju@mpfi.org

Bio

Dr. Vidhya Rangaraju started her Research Group Leader position at the Max Planck Florida Institute for Neuroscience in January 2020. The overarching goal of the Rangaraju group is to investigate the energy use and supply of biological processes in neurons.

Prior to this appointment, Rangaraju was an EMBO and Marie Curie Postdoctoral Fellow in the group of Dr. Erin Schuman at the Max Planck Institute for Brain Research in Germany. During her postdoc, she uncovered the presence of local mitochondrial compartments of energy that fuel local translation during synaptic plasticity.

Rangaraju completed her Ph.D. in the lab of Dr. Timothy Ryan at Weill Cornell Medicine in New York. During her graduate work, she developed a novel optical reporter of synaptic ATP to measure dynamic changes in ATP concentrations and elucidated the link between neuronal activity and ATP synthesis.

She is the recipient of numerous awards, including the Vincent du Vigneaud Award of Excellence, Lindau Nobel Laureate Meeting Award, the MPIBR Scientific Discovery of the Year Award, the SfN Peter and Patricia Gruber International Research Award, and the CZI Ben Barres Early Career Acceleration Award.

 

 

Research Topic

The Neuroenergetics Lab is interested in how neurons, with their unsurpassed morphological complexity, manage their energy landscapes. Neuronal function is tightly regulated by its metabolic state. Mitochondria, the major energy source, represent a hugely underexplored organellar system in neurons. This lack of knowledge has real consequences for human health, as mitochondrial proteins are hotspots of dysregulation in neurodegenerative diseases.

Current Projects

Spatial stabilization mechanisms of mitochondria

Using APEX-based proximity labeling and advanced imaging to quantify mitochondria-actin interactions, we have identified spatial stabilizers of mitochondria in neuronal dendrites. We have discovered a distinct role for the ALS-linked protein VAP in stabilizing mitochondria within dendrites for long durations of plasticity and for fueling learning, memory, and development in spines (Bapat et al. Nature Communications 2024). We are now investigating the significance of mitochondrial stabilization, local energy supply, and its disruptions in motor and cognitive impairments in ALS.

 

Local mitochondrial ATP production and spine bioenergetics during synaptic plasticity

We have developed novel spine- and mitochondrial-ATP reporters and a custom microscope to image ATP within single spines and individual mitochondria during synaptic plasticity. We dissect the molecular mechanisms driving mitochondrial ATP synthesis in response to spine plasticity induction. We also determine how spine ATP levels are impacted at different stages and forms of synaptic plasticity, identify the ATP consumers, and discover novel temporal regulators of ATP synthesis during synaptic plasticity.

 

Ultrastructural remodeling of mitochondria and ribosomes during neuronal plasticity

We have developed a correlative light and electron microscopy (CLEM) pipeline to combine functional spine, mitochondrial, and ATP imaging with transmission electron microscopy, electron tomography (ET), cryo-ET, and DNA-PAINT to characterize mitochondrial ultrastructure and ribosome recruitment during neuronal plasticity. This project will reveal the structural adaptations of mitochondrial cristae, ATP-synthesizing-complex assemblies, and mitochondria-ribosome associations and uncover novel features that support various forms of neuronal plasticity.

 

Mitochondrial biogenesis in neuronal compartments

We hypothesize that neuronal compartments have the raw materials required for mitochondrial biogenesis. We will generate a mitochondria-and-cytosolic-RiboTag mouse and employ advances in ribosome profiling, RNA sequencing, and metabolic labeling of nascent proteins to identify locally translated mitochondrial transcripts. We will determine the mechanisms that control the local replenishment of the mitochondrial proteome to cope with plasticity demands.

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