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Savoring the Individuality of a Cell
Mandovi Chatterjee and her team uncover the secrets found within a single cell
To describe the difference between bulk and single cell RNA sequencing, Dr. Mandovi Chatterjee compares a fruit bowl to a smoothie. “When you’re drinking a smoothie, the taste you are getting is an average taste of all the fruits,” she begins, “you cannot detect the individual taste of any fruit.” That’s where things get interesting.
Now, if you pick one fruit from the bowl and savor it, and then try another, you can distinguish the individual tastes,” she continues, “that is sort of the equivalent of single cell RNA sequencing.”
That is what Mandovi does in her role as Director of Single Cell Core at Harvard University Medical School. By diving in and picking a specific cell, Mandovi leads a team that studies tissues at a single cell level—savors the individuality—in great detail.
In a human body consisting of trillions of cells, disease can originate from a single mutation in a single cell. Using the example of a recurring cancer, “Had the primary tumor been studied by single cell RNA sequencing, which has the advantage of detecting a rare cell type,” she says, “ it would have been able to detect that rare population in the first place.” She adds that it may also have changed the trajectory of the original treatment.
Over the past decade, innovative integration in the use of microfluidics paved the way for expansion of single cell research. “The introduction of microfluidics enabled studying tens of thousands of cells per sample, in a cost-effective way and reasonable timeframe,” Mandovi added.
Further gains have been made with the introduction of next-generation sequencing (NGS). Mandovi asserts that NGS has also made this work more economical. “Once you barcode thousands of cells, you need to sequence them,” she continues, “The amount of data generated from thousands of cells makes it cost effective.”
Relying on averages, as in traditional approaches to research, often falls short in cases such as the aforementioned cancer example. “We know that every single biological process depends on cell-to-cell interaction,” she states, “and the response depends on what is coming from neighboring cells. So, we are missing a lot of information that can only come when studying a single cell in its spatial context.”
This leads to what Mandovi sees as the next big advance in single cell analysis—spatial transcriptomics. “Spatial transcriptomics bridges the gap between single cell RNA sequencing and studying cell behavior in situ,” she adds. The Single Cell Core Lab supports research in a variety of disciplines and relies on the need to constantly adapt and modify. Mandovi and her team often have the opportunity to apply technology in ways that might not occur in other labs. One example is the study of non-model organisms. “You always have to adapt those technologies in a way that is compatible with non-model organisms,” she emphasized. “We often have to change something in an established protocol,” she continued, “And we always try to push the limit of every single technology to accommodate more samples or more cells.”
Finding a mutation in one specific cell may seem impossible, but that is what drives Mandovi's team. “When a disease happens, that can happen due to a single mutation in one cell,” she said. This drive to identify the roots of a disease came from an early age. Mandovi was inspired by her parents, who were both physicians, and aspired to be a doctor when she was a child. “I was exposed to the world of diseases early on,” she states, “Discovering or designing a drug, and how that could help treat certain types of disease was something that I found very exciting.” Outside of the lab, Mandovi enjoys birdwatching—a pursuit she was introduced to while working on her Master’s in Zoology. During that time, she was able to experience first-hand the biodiversity of several forests in her native India and it ignited a passion she now shares with her daughter.
For a deeper dive into Mandovi Chatterjee’s work, check out her interview on Speaking of Mol Bio. There we learn more about her career trajectory, her work at the Single Single Cell Core at Harvard Medical School, and how Single Cell Analysis is an interdisciplinary pursuit.
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