Rahul Satija: Single Cell Genomics

Tell me about your position at the New York Genome Center.

I run a research lab at the New York Genome Center, which opened about 10 years ago. It’s a nonprofit institution with a strong focus on new technologies in genomics and computational biology. There are a number of faculty labs here, and we're spread across all over New York. There are some faculty labs that are jointly affiliated with NYU, like mine, but others with institutions like Columbia or Weill Cornell Medicine. It's meant to be a city wide initiative, to synergize and collaborate around really cutting-edge advances in DNA sequencing, which is what my lab works on.

We're right in downtown Manhattan, and all of us are really interested in trying to use technologies based on DNA sequencing to improve human health. I was one of the early faculty members here, so to get to kind of build that center has been a lot of fun.

What kind of research is your lab working on?

We're very interested in this new field called single cell genomics, which is where we can take technologies for DNA sequencing, like genome sequencing or RNA sequencing, but instead of applying them to samples that consist of millions or billions of cells, we want to apply them to one cell individually at a time. So this can be really valuable in really any organism. But for example, in the context of a human being, where all of our organs–our brain, for example–may consist of tens of thousands of different types of cells. If we do experiments on all of the cells together, we get a very different result than if you can look at them one at a time. So this ability to do genomics at single cell resolution–it's sort of a new type of microscope. And there are a lot of very wide applications throughout many fields of biology.

So my lab does a lot of things with single cell genomics: We're interested in developing new technologies for sequencing. We're interested in developing software and computational methods that people can use to analyze that type of data. And we work very closely with biological collaborators in developmental biology, immunology, or neuroscience, to answer their questions using some of the tools and technologies that we develop. So it's a really nice balance, but it is really all enabled by these new technological advances.

Is there any recent research that you are excited about–that you can share?

There are a few things that are unpublished, but one thing that has been particularly exciting, especially working in this kind of new technology field–the first papers are very methodologically driven, because they're really trying to report on technological advancements. But then, as the field starts to mature, you start to use those types of approaches to really discover new things. And so my lab now more and more in the last couple of years, is focusing on things that we're learning and discovering, in addition to the new technologies that we're developing.

Some of the results that I'm really quite excited about–some of which is published and some of which we're getting ready to share–relate to identifying particular populations of cells that may be important for providing long term immunity during COVID vaccination (Cell, 2021). We've also identified particular genes in the developing mammalian brain that are important for specifying what type of neuron a cell is going to become (Nature, 2018). We've identified particular genes that are important or that work together in the context of promoting cancer differentiation (Nature, 2016), and we're thinking about ways to to broaden the applicability of those results (bioRxiv). So it's been fun–we work on a lot of different things, but we're starting to have more of a biological focus as our field matures. And that's been very satisfying.

Your lab has a tool called Seurat–can you tell me what that is?

Seurat is a software package that I started developing when I was a postdoc at the Broad Institute at Harvard and MIT. And now my lab develops and maintains it. Seurat is a software package that you can use to analyze and explore and interpret data from a single cell sequencing experiment. Because the field has really grown tremendously over the past decade, biologists needed tools and software to be able to analyze their experiments. So we had a fun opportunity to have a lot of impact in the community by developing some of these tools.

Seurat is one of many software packages that people use, and it is downloaded something like 40,000 times each month so we have a wide user base of biologists in all sorts of different fields–cancer immunology, developmental biology, neuroscience, evolutionary biology–who are running these types of experiments and looking for ways to analyze their data. It's been a fascinating opportunity for us to see how the world is using these types of tools and technologies through our software. And we named it Seurat because many of the visualizations or analysis plots that we make plot individual cells, and they look like little dots that are reminiscent of pointillism paintings from artists like Seurat.

Your lab also runs an annual conference on single cell genomics–can you tell me more about that?

Single Cell Genomics Day is a yearly, free and open conference that we do–and now we livestream it entirely online, on YouTube. And the reason we started it was because we felt like the field was changing so much every year. In biology generally and especially in genomics, every year there will be some new technology, whether it's genome engineering with things like CRISPR, or whether it's single cell genomics. And it's not just one advance where everything changes–it's a continual series of advances. And it's not by only one group–it’s from people all over the world.

It can be really intimidating if you're a biologist who wants to use these tools to know what the state of the art is. So we design our workshop as a way to update the field on research and tools that we think are really interesting and valuable, and there has been a lot of excitement and interest from the community. We have thousands of people tune in every year, and it's a great opportunity to celebrate a lot of advances that have come from across the entire community every year. And it's really fun that we're able to do it in a free and open source way. We have a number of funders, including the Chan Zuckerberg Initiative, and the National Human Genome Research Institute, which enable us to do that.

What does it mean to be free and open source?

There's a real trend now in biology and in scientific research in general to try to do open science, which can mean a lot of things. For example, Seurat is published under a fully open source license, so it's free for anybody to use. The code is also fully available, so anyone can see exactly what we're doing and make modifications as they would like. It also means that when we release papers, we aim to release data openly, in a way that people can reuse and reproduce our results. In addition, when we release papers, before we publish them in peer reviewed journals, we put them on preprint servers like bioRxiv where they can be freely accessed by anybody.

This all goes towards the goal of keeping science open and free. A lot of our money comes from charitable organizations and from public organizations like the NIH. So when it’s possible, if there's an ability for us to release something openly, we love to be able to do that. With Single Cell Genomics Day, for example, we could have charged a fee, but we really just want anybody to be able to tune in and listen if they're interested. And again, we're lucky that we have people who are willing to sponsor that and fund that goal.

You got your PhD at Oxford. What was it like to be at Oxford as a Rhodes Scholar?

It was really an extraordinary experience and opportunity for me to live abroad and to do my PhD in England–for me it was an entirely new experience. The people that you get a chance to meet–both at Oxford and also as part of the Rhodes program–really changed my life in so many wonderful ways. I met my wife there–she was a Rhodes Scholar from India, and we were in the same Residential College.

Oxford is also an incredible place for independent music. Radiohead came out of Oxford, and there's a really rich scene of new bands that are up and coming. I was a classical violinist, but I wound up connecting with a folk rock group called Stornoway (YouTube) when they were kind of a small band, and I wound up touring all over the world with them for a few years. So really, it was a life changing that just had a huge impact on my career and my life–so I'm really grateful for that.

What about your experience in the Blair Magnet? Are there any classes or activities from Blair that had a particular influence on you?

There are many classes that I remember and had a positive influence on me, whether it was Physics with Mr. Bunday and Mr. Donaldson or Computer Science with Ms. Piper.

But I think the class that had the most impact in terms of what I got really excited about and chose to pursue was Genetics with Ms. Bosse. I think she's still there and continues to have a tremendous influence on people going into this field–all the alumni that I have talked to in our field remember that course, and she was really inspirational. I don't think a lot of high school students get the opportunity to really learn and get excited about cutting edge research in genetics and genomics at that age, and I was really fortunate for that.

And the other class that I remember really well is Functions with Ms. Dyas, which I took as a freshman. I have never taken such a difficult course in any other context, and, but it was quite a learning experience for me, and I grew a lot during my freshman year at Blair.

Is there anything else you would like to share with the Blair Magnet community?

I would say two additional things: The first is that we are thinking a lot now about how to improve representation and inclusivity in science. And as part of that conversation in our lab, we thought about what got us excited about research and what kind of set us on these paths. And I think everybody identified a particular teacher or a particular mentor that had played a role in pushing them towards where they are now. And so I think all of the teachers at Blair know this, but they can have an incredible impact on shaping our long term careers, and they did for me.

The other thing I would like to say is to thank David Ngbea, who coached the tennis team. I played one singles for Blair, which meant that every week I would play the best person on whatever team we were playing–and Montgomery County is a very good place for tennis so it was pretty tough sledding every year. Tennis is an individual sport and the competition can build mental toughness, but Mr. Ngbea created a really enjoyable community for the team.

Interview by Ted Jou '99