Cells within a tissue or organ may appear very similar, if not identical. However, at the molecular level, these cells can have small differences that result in wide variations in their functions; this is the challenge addressed by US scientists, who develop and apply technologies such as single-cell RNA-sequencing (scRNA-seq), which allows the researchers to analyse variations in gene expression patterns and determine how each cell contributes to the operation of a tissue.
“Single-cell RNA-sequencing is an incredibly powerful way to examine what cells are doing at a given moment. By looking at associations among the different mRNAs that cells express, we can identify really important features of a tissue-like what cells are present and what are those cells trying to do,” says Alex K. Shalek, an associate professor of chemistry at the Massachusetts Institute of Technology (MIT).
While his research focuses on identifying small-scale differences, he hopes that it will have broader implications as he seeks to better understand globally important diseases like HIV, tuberculosis, and cancer.
Shalek has been driven to connect science to human health and understand what is happening in various diseases to develop better preventions and cures, thus, he’d notice differences in mRNA levels, or in protein expression or activity.
Instead of doing pooled sequencing of mRNA, he began to wonder if it would be worthwhile to study each individual cell within a system. During his postdoctoral fellowship, he worked to develop technologies for sequencing all the mRNA found in large groups of individual cells. This information can then be used to categorise cells into different types and reveal their current state.
Shalek now uses improvements he helped make to this approach in his lab at MIT to analyse various types of cells and tissues and study how their identities are shaped by their environments. His most recent research has focused on how cancer cell state influences chemotherapy response, the cellular targets of the SARS-CoV-2 virus, the cell types involved in lactation, and the classification of T cells primed to generate inflammation during allergic reactions.
This work’s overarching theme is how cells maintain homeostasis or the constant state of physical and chemical conditions within living organisms. On the other hand, Shalek emphasised the importance of homeostasis because he knows that imbalances can lead to autoimmune diseases and immunodeficiencies, as well as cancer growth. He wants to define what balance is at the cellular level, how to maintain balance, and how various environmental factors such as exposure to different infections or diets alter that balance.
Shalek expressed gratitude for the numerous opportunities he must collaborate with other researchers at MIT and in other areas, in addition to his many international collaborators. As he works on human disease problems, he ensures that the next generation of scientists receives the same training and mentoring that he did as a graduate student and postdoc.
He stated that his experience taught him the importance of supporting and empowering scientists, as well as trying to uplift the community, and he acknowledges that a large part of his success is due to people who assist him. “If you put together the collective brain trust of this community, as well as partner with people all around the world, you can do incredible things.”
