Not lost in space Episode #2
Play • 41 min

This podcast is with Dr. Hongkui Zeng who directs the Allen Institute for Brain Science and Dr. Bolisjka Tasic who directs Molecular Genetics at the Allen Institute for Brain Science. It’s about how spatially resolved transcriptomics, a Nature Methods Method of the Year, can help to understand the brain. I did a story about it here: https://www.nature.com/articles/s41592-020-01033-y .

This is a podcast series that shares more of what I found out in my reporting. The piece is about smoothies, fruit salads, fruit tarts, genomics and a big puzzle called: the brain.

Transcript of podcast
Note: These podcasts are produced to be heard. If you can, please tune in. Transcripts are generated using speech recognition software and there’s a human editor. But a transcript may contain errors. Please check the corresponding audio before quoting.

Not lost in space Episode 2

 

Hi and welcome to Conversations with scientists, I’m Vivien Marx. This podcast is about space--space in biology, actually.

 

Talking about the role of space and spatial analysis in biology is a chat about food. About smoothies, fruit salads and fruit tarts. Here’s Dr. Hongkui Zeng and Dr. Bosiljka Tasic from the Allen Institute for Brain Science.

 

[0:30] Bosiljka Tasic 

Fruit salad and smoothie. 

Fruit tart is spatial transcriptomics.

Smoothie is Bulk RNA-seq. Ok passé

 

Hongkui Zeng

Forget it. 

 

Bosiljka Tasic 

You have fruit salad, you have dissociated cells you are profiling, you have lost the context, you have a context in the piece of tissue you have dissected. 

Then there is the fruit tart. You know exactly where each piece of fruit.  Relationship to the other

 

Vivien

Ok so spatial analysis in genomics is understanding a fruit tart. Knowing which genes are expressed where and what the relationship is of the genes to one another. The two scientists will talk more about this shortly. There’s Dr. Bosiljka Tasic, she directs Molecular Genetics and her research is for example on cell types in the mouse brain. And Dr. Hongkui Zeng who is director of the Allen Institute for Brain Science. Before they explain more about this science, here they both are, kindly teaching me how to pronounce their names. As ever I will try to do this right. And likely fail. 

 

[1:37] Bosiljka Tasic and Hongkui Zeng

I'm Bosiljka Tasic. Bosiljka Tasic. OK, got it 
 
 Hongkui Zeng. You don't pronounce the G at all, just, well, Zen, yeah, Zen G Zen. Yeah, yeah. It's very, very almost not there. 
 
 How would you how would you pronounce that if you emphasize the G . ZengG. So I think g you hear much more but it's not the correct way. I mean I've given you my Americanized way of saying my name. I see. Well I'm going to, I'm going to do it wrong anyway. But but at least for me, don’t  worry.

 

Vivien

Next, before we get back to their thoughts and research, just a bit about this podcast series. 

 

In my reporting I speak with scientists around the world and this podcast is a way to share more of what I find out. 

 

This podcast takes you into the science and it’s about the people doing the science. You can find some of my work for example in Nature journals that are part of the Nature Portfolio. 

 

That’s where you find studies by working scientists and those are about the latest aspects of their research. And a number of these journals offer science journalism. These are pieces by science journalists like me. 

 

This podcast episode about space in biology harkens back to interviews I did  months ago. Back then I asked scientists about their work and their thoughts about spatially resolved transcriptomics, which is a Nature Methods method of the year. In my slow pokey DIY podcast production this is episode 2 in a series about this field of study. 

 

Spatially resolved transcriptomics helps with studying the brain, which is the giant puzzle that Hongkui Zeng and Bosiljka Tasic work on. Among their daily puzzles is: How many different cell types are there in the brains of mammals such as mice, primates or humans? There are lots of them.  

 

And scientists want to be more precise than just saying there are lots of cells, of course. They want to know which ones there are and where they are. 


In the brain, another puzzle is where are cell types when. Cells are born and then often move to other areas of the brain where they will tend to all sorts of tasks. It takes a number of techniques to address these questions, including spatial techniques. 

 

The US National Institutes of Health—NIH--has many research projects, one of them is the Brain Initiative, NIH's Brain Research through Advancing Innovative Neurotechnologies Initiative. 

 

Part of that is the NIH Brain Initiative Cell Census Network (BICCN). One big BICCN project is to build a high quality atlas of cell types in the entire mouse brain. 

 

Many labs are working together to produce human, mouse and non-human primate brain atlases, these are intended as references for labs around the world. The scientists use imaging, electrophysiology and molecular genetic analyses including analysis of gene expression, which is transcriptomics. 

 

BICCN phase 1 is underway and phase 2 is getting underway. The project has started with the mouse brain and is moving toward an atlas of the non-human primate brain and the human brain. 

 

One big challenge in this venture is distinguishing cell types. Cells may look very different but they might also look quite similar to one another. Here is Hongkui Zeng talking about BICCN

 

[5:20] Hongkui Zeng

We are currently in phase one, BICCN phase one, building this brain-wide cell type reference atlas. We are doing quite well and we expect to complete phase 1 in the next two years. And then phase 2 is starting, BICCN, phase 2 what you heard at SfN. There are several major themes for phase 2 that were announced by NIH. 

The three major themes are building cell-type targeting tools, moving into the study of primate brains including human brain, cataloging cell types in the human brain and then finally studying the connections, the connectomics of the human brain. 

Bosiljka is very active in one of those initiatives, which is building in one of cell type targeting tools 

 

Bosiljka Tasic 

You want to define a cell type first, but then you want to be able to access it for experimental examination perturbation. You want to form causality connections between a cell type and, let's say a specific behavior. So in order to do that, you need to build usually a genetic tool that is based on genes that are expressed in the cell type or maybe regulatory elements, enhancers that are active in that cell type. You can you can create a transgenic mouse or a viral tool that will then deliver a particular transgene, a particular perturbing or labeling gene to that cell, and then you can visualize the cell, monitor it, maybe monitor its activity or perturb it and ask for 
 Phenotypes effects at the level of that cell, at the level of the circuit, at the level of the whole organism.

 

And both Hongkui and I, we are we have a just...

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