about

Currently, I work on the structure and function of complement component 1q-like (C1QL) proteins, which help neurons in the brain form and maintain the chemical junctions between them. My work in the Ressl lab aims to understand how these proteins assemble into the complexes that engage their receptors which are genetically linked to schizophrenia, bipolar disorder, and addiction. Because so many approved drugs act on this family of receptors, a structural picture of this interaction could point toward new treatments for psychiatric disorders that remain difficult to manage.

Figure 1. / Left, a close-up of the chemical junction called a synapse boxed at right, where the end of one neuron meets the start of another. C1QL proteins freely exist in the junction and anchor both sides of the junction through velcro proteins. One side binds to a cell surface receptor on the receiving side, lining the two sides of the junction up and gathering other proteins around the receptor, while its other side holds onto velcro proteins on the sending side. Other C1QL proteins are captured by a different set of velcro proteins and bind ion channels on the receiving side to form the chemical junction. When these channels open, they conduct ions to allow signals to pass between neurons. The receptor that C1QL proteins bind to on the left belongs to a superfamily that is the target of roughly a third of approved drugs.Left, a close-up of the synapse boxed at right, where an axon terminal of one neuron meets a dendritic spine of another. C1QL trimers pair into hexamers that are secreted into the synaptic cleft and anchor to the presynaptic membrane. One binds the N-terminal domain of an adhesion G protein-coupled receptor (aGPCR), aligning the postsynaptic membrane with the presynaptic membrane and organizing the proteins around the receptor, while its other end is held presynaptically by a neurexin or pentraxin. Others are captured by presynaptic neurexin-3 and bind kainate receptors (KARs), tetrameric ionotropic glutamate receptors, then link into higher-order assemblies (here an 18-mer) that cluster KARs at the synapse; these channels open on glutamate binding and conduct monovalent cations (Na⁺ flowing in, K⁺ flowing out) and, in some subunit forms, divalent Ca²⁺. aGPCRs belong to the G protein-coupled receptor superfamily, the target of roughly a third of approved drugs.

I also collaborate with the Callmann group by using molecular dynamics simulations to determine how a glycopolymer we make can help poorly soluble medicines reach patients. Sugar-based polymers like ours are increasingly explored as drug carriers that could allow lower doses with fewer toxic side effects.

Figure 2. / Many medicines slip through the outer layer of a cell easily, but before they get the chance, they clump together in water and little reaches its target. A single chain of ten sugar-carrying building blocks wraps around one medicine molecule and pulls it free. The backbone of the chain hugs the medicine while the sugars face outward and mix with the surrounding water. The cell swallows the wrapped medicine. Inside the cell, the chain lets go and the medicine binds the protein it was designed for.Many drugs are hydrophobic: they cross cell membranes readily but barely dissolve in water, so on their own they clump together and little reaches its target. In our simulations, a glycopolymer 10-mer wraps around a single drug molecule. Its hydrophobic backbone packs against the drug while the glucose on each of its ten repeat units faces outward, where the hydroxyl groups hydrogen-bond with the surrounding water. The cell membrane takes up the wrapped drug by endocytosis. Inside the cell, the polymer releases the drug, which binds its target protein.
past

Most recently, I worked on the structural biology of phospholipase C epsilon (PLCε), a signaling protein frequently dysregulated in cancers. This work was part of a larger effort in the Falzone lab to understand the regulatory role of phospholipases in cellular signaling pathways and how these mechanisms may eventually be targeted therapeutically.

Figure 3. / Left, ligand binding activates a cell surface receptor and through a currently unknown process that involves binding to other cancer-associated proteins, the receptor eventually brings PLCε to the membrane, where it splits the molecules in the cell membrane into head and tail messengers. Right, the same pathway in a whole cell: the head frees calcium stored inside the cell and the tail calls in another signaling protein, signals that end up triggering the growth and division of a cell. The full-length structure of PLCε is unknown, so it is drawn as a blob. One can see how an overexpression of PLCε can lead to cancer, defined as uncontrolled cell growth and division.Left, ligand binding activates a GPCR, and the activated G protein relays a signal (through small GTPases, omitted here) that brings PLCε to the membrane, where it hydrolyzes PIP₂ into the second messengers IP₃ and DAG. Right, the same pathway in a whole cell: IP₃ releases Ca²⁺ from the endoplasmic reticulum and DAG recruits protein kinase C (PKC), signals that converge on cell growth and division. The full-length structure of PLCε is unknown, so it is drawn as a blob.

Before that, I was a software engineer at Hack Club Bank, where I was part of a small team of developers that helped build a financial platform for students and nonprofits to raise and manage finances transparently. Prior to that, I was a designer-developer at Hack Club, where I helped build tools and experiences for students to build projects and learn to code.

I attended the University of Texas at San Antonio, where I earned a BS in biochemistry and focused on biosynthetic organic chemistry and computational biophysics. I am grateful to have gotten my start in research in an organic chemistry group on campus. I also learned small molecule X-ray crystallography from Dr. Hadi Arman at that time. After those experiences, I continued my research career working with Dr. Maria Falzone and Dr. Rahul Mojidra on the structure and function of PLCε using cryo-electron microscopy and fluorescence spectroscopy. For my thesis, I worked on mathematical methods to improve macromolecular structure modeling from cryo-EM density maps. I was co-advised by Dr. Maria Falzone and Dr. Hadi Arman for this work.

Figure 4. Left, density functional theory (DFT) on an aromatic ketone: the electron density converges over self-consistent field iterations, then the HOMO and LUMO appear as an electron is promoted between them. Middle, small-molecule X-ray crystallography: a rotating crystal diffracts X-rays onto a detector, and the solved structure is drawn as thermal ellipsoids. Right, single-particle cryo-EM: particles picked from a micrograph are aligned and averaged into 2D classes, which are oriented in 3D to reconstruct a consensus map; a model is then built into the map, with open circles marking low-confidence residues.
research
A Map-Only Framework for Predicting Residue Placement Confidence During Cryo-EM Model Building
Mohanty, S.1 (2026), undergraduate thesis, in press
Matrix-Based Protein–Protein Interaction Screening and Region-Aware Interface Analysis Mohanty, S.1,2,3,4 (2026), software
Enhanced 2-Hydroxyglutarate Production by the IDH1 R132G Variant Reveals Differential Neomorphic Gain-of-Function Among Glioma-Associated Mutations
Mohanty, S.1, Marrs, K.1, & Thomas, S.1 (2026), manuscript in preparation
Functional Characterization of PLCε Catalytic Activities
Mohanty, S.1,2,3,4, Mojidra, R.2,3, & Falzone, M.2,3,4 (2026), poster, manuscript in preparation
A Reproducible Web Workflow for Plate-Reader Data Normalization, Kinetic Modeling, and Reporting Mohanty, S.1,2,3,4 (2025), software
Optimization of Full-Length PLCε Purification to Enable Studies of Ras-Mediated Oncogenic Signaling
Mohanty, S.1,2, Mojidra, R.2,3, & Falzone, M.2,3,4 (2025), poster
Formal Languages and Compiler Tools for Burden-Aware Genetic Circuit and Pathway Design
Mohanty, S.1 (2025), proposal
A Telemetry Pipeline for Quantitative Longitudinal Pattern Tracking in Chemical Education Mohanty, S.1 (2025), software
1Department of Chemistry, University of Texas at San Antonio, 2Department of Biochemistry and Structural Biology, UT Health Science Center San Antonio, 3Greehey Children's Cancer Research Institute, San Antonio, TX, 4Mays Cancer Center, San Antonio, TX
email
hello [at] sarthakmohanty [dot] me