The power of single-cell analysis

Renee Shenton
Breakout Ventures
Published in
5 min readOct 20, 2021

At Breakout Ventures, we believe cells are the engine of the next decade as the tools, technologies and, most importantly, talent from across industries are brought to bear on biology and chemistry in surprising ways.

We partner with bold entrepreneurs building a bio-based future and invest in creative bioscience companies harnessing the power of cells and computation to scale solutions in human health and sustainability.

We are excited to introduce you to CellChorus, the first seed investment out of our new fund. CellChorus conducts comprehensive dynamic single cell analysis at scale.

While several companies have advanced single-cell analysis in recent years, mostly with static modalities, CellChorus is the only company that provides live imaging of single cells. Single-cell analysis is a technology that has influenced various –omics level data sources and live imaging is primed to undergo this same revolution.

We sat down with Chief Scientific Officer Dr. Navin Varadarajan to learn more.

Breakout Ventures (BOV): Navin, welcome to the Breakout Ventures family! Let’s dive right in — you are considered a pioneer in multiple molecular and cellular technologies for immunotherapy. Can you tell us a bit about your background?

Chief Scientific Officer Dr. Navin Varadarajan

Dr. Varadarajan: I have training in many different fields. My undergraduate and Master’s degrees are in Chemistry from India, my PhD is in Biochemistry from UT Austin, and m postdoctoral training was in Immunology at MIT.

In addition to being CSO at CellChorus, I am currently the M.D. Anderson Professor of Chemical and Biomolecular Engineering at the University of Houston, where my Single Cell Lab focuses on developing high-throughput screens designed to characterize a wide range of biological functions, from the properties of proteins in single cells to antigen mediated cellular cytotoxicity.

My path has obviously been non-linear, but I am fortunate to have always worked with diverse groups of people who motivated and challenged me to explore new fields of investigation beyond my background and training. As a result, I have a unique perspective on providing researchers with a comprehensive understanding of their cells.

BOV: I understand the technology that CellChorus was founded on was developed in your Single Cell Lab. What was that technology and how does it integrate with CellChorus?

Dr. Varadarajan: Single cell is the unit of definition in cell biology. The importance and impact of studying cells at single-cell resolution has matured in the last ten years and assays like single-cell RNA-sequencing are now standard.

Despite these advances, there are limitations in how we study dynamic cell biology. Nucleic acids (DNA and RNA) are amplified easily and hence single cell technologies quantifying nucleic acids have been developed rather quickly. By contrast, understanding the dynamics of cells and how they move, change, adapt and evolve to their microenvironment — and how they interact with other cells — is very difficult to study. My lab, very early on, recognized the importance of dynamics. Cells are constantly changing and it is their functional capacity, rather than the abundance of nucleic acids or proteins that defines them. Our TIMING (Time-lapse Imaging Microscopy in Nanowell Grids) platform parallelizes thousands of single-cell interactions such that scientists are now able to watch each cell live its own life.

TIMING has served my lab admirably to study immunotherapy and enabled me to perform meaningful work such as engineering more potent immune cells for cancer immunotherapy. We have a decade’s worth of intellectual property associated with our approach, including the algorithms and associated data from studying millions of immune cells and their interactions. If TIMING is more widely accessible, scientists worldwide can make their own discoveries in dynamic cell biology and design their own cell-based therapies.

CellChorus aims to bridge this gap by commercializing the technology. We provide scientists new insights into their cells that reveal behaviors they did not fully appreciate. The best part about TIMING is that it is complementary to several mature single-cell technologies. Data from TIMING can be linked to single-cell sequencing and other techniques.

BOV: What are some of the applications for the CellChorus platform?

Dr. Varadarajan: Our initial focus is on immunotherapy, specifically adaptive immunity. Immune cells are motile (moving 10 microns/minute) and are poised to patrol essentially every part of the body. They execute a variety of functions including terminating invading pathogens and infected or cancerous cells. These properties of immune cells are dynamic and regulated upon encountering the appropriate threat.

This adaptable behavior of immune cells makes them challenging to study but also presents an opportunity. The CellChorus TIMING platform is uniquely poised to study immune cells and we believe it is a game changer for at least three reasons:

  • Throughput: Unlike other assays, we can profile the dynamic behavior of thousands of cells.
  • Complementary: Our assays are non-destructive to cells, and so can integrate with other single-cell assays allowing for multi-omic profiling.
  • Sample conserving: Our platform can work with as few as 10,000 cells ensuring that we can evaluate small populations of cells directly derived from patients.

BOV: Why is live cell imaging so important?

Dr. Varadarajan: Not only are cells dynamic, but their behavior is altered in the presence of other cells. Being able to profile cell dynamics at single-cell resolution ensures that we can eliminate guessing and pseudo-time analyses. We can directly watch the cells in action and then study additional properties of the same cell. Live cell imaging with single cell resolution ensures that you have the best of both worlds: you know the functions of the cell and you can map additional features onto the same cell.

BOV: What technical milestones do you hope to achieve in the next six months?

Dr. Varadarajan: We are preparing some exciting announcements with existing customers and partners that will showcase the value of the TIMING platform; we just can’t say much yet!

About Breakout Ventures

Breakout Ventures is the home for creative bioscience entrepreneurs. We challenge the traditional boundaries of science to unlock new possibilities.

We invest in Seed and Series A-stage companies building bio-based solutions that will substantially impact human health and sustainability.

Breakout Ventures was founded in 2016 and based in San Francisco, California. Visit us at https://breakout.vc.

Breakout Ventures. Building a future powered by science.

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