Ankit Basak (Chemistry/IMES)
When Ankit Basak arrived at MIT for graduate school, he came with a broad, interdisciplinary background and a keen interest in developing new tools for biological research. Raised in Kolkata, India, Basak pursued an integrated BS-MS program at the Indian Institute of Science Education and Research (IISER) Kolkata, where he studied chemistry and biology. From the start, he was drawn to technology development, and worked on wide-ranging projects, including synthesizing perovskite nanowires for optoelectronic applications, developing organic fluorescent sensors for detecting iron ions in water, and designing algorithms to accelerate MRI data acquisition.
That appetite for methodological innovation has carried through to his doctoral work at MIT, where Basak is a fifth-year PhD student, co-mentored by Professors Laura Kiessling (Chemistry) and Alex Shalek (IMES). His research now tackles a central question in microbiome science: how do human cells recognize different microbes and distinguish whether they are friend or foe?
Much of that recognition is mediated by glycans — complex sugar molecules decorating cell surfaces — and lectins, the glycan-binding proteins on host cells. However, the ability to study these interactions in their native environment — the mucosal barrier tissues that line our digestive, respiratory, and other tracts — has historically been out of reach. Traditional glycan profiling methods rely on ex vivo assays using cultured cells or small pieces of tissue, and measure bulk samples. They lack the single-cell, spatial detail needed to understand how recognition happens in the mucosal tissue environment.
Basak has addressed this gap by co-developing a platform called GOAT-seq (Glycan Outlining And Transcriptome sequencing). The method uses DNA-barcoded human lectins as molecular probes. When applied to single-cell or spatial transcriptomic workflows, the barcodes allow researchers to simultaneously capture glycan-binding profiles and gene expression readouts. “This means we can finally ask, in a tissue context, which host and microbial cells are binding to which lectins, and which transcriptional programs accompany that binding,” Basak explains.
He has already have validated these methods for profiling host cell glycans and transcriptomes. The next step is to integrate the platform for microbial single cell and spatial transcriptomics. The biggest challenge, he says, “is that bacteria have so little mRNA. It’s very hard to get a robust readout of genetic information.” His strategy is to optimize workflows for expressing recombinant human lectins, which bind more effectively to microbial surfaces than the plant lectins typically used in research. By barcoding these human lectins and integrating them into single-cell and spatial sequencing platforms, he aims to capture not just the genetic programs of microbes but also their glycan signatures and their recognition by host immune proteins.
While the platform could be used in a wide range of disease areas, Basak is currently focusing on periodontitis, the chronic inflammatory gum disease that affects nearly one in five people worldwide. “Periodontitis is fascinating because it’s really about dysbiosis,” he says. “There’s a complex interplay between the microbial side and the host side that together drive the disease.” The implications extend well beyond oral health, he notes. Periodontitis is now linked to diseases including gastrointestinal cancers, type I diabetes, cardiovascular disease, rheumatoid arthritis, and even Alzheimer’s disease.
“My goal is to use this new method to understand the microbial and host factors that mediate glycan/lectin interactions, so we can find therapeutic targets against this devastating disease.”
“Fusobacterium nucleatum is anoral bacterium but we now know it can cause colorectal cancer,” he explains. “And a lot of Alzheimer’s patients start with periodontitis. People have found bacterial proteins in their brain tissue — proteins that aren’t supposed to be there. It’s likely that when there’s inflammation, a leaky mucosal surface in the mouth allows bacteria to enter the bloodstream and migrate to these other sites.”
For Basak, these connections highlight the need for technologies that allow scientists to probe host/microbe interactions at high resolution, in their native tissue environment. Ultimately, he hopes to pursue an academic path that continues to blend technology development with biological discovery. For now, though, his focus is on unraveling the conversations between human cells and microbes in the mouth. “My goal is to use this new method to understand the microbial and host factors that mediate glycan/lectin interactions, so we can find therapeutic targets against this devastating disease.”
