Follow Your Nose – Even in the Lab

Debby Silver’s lab at Duke University uses a two pronged approach to better understand how the brain forms. As a Primary Investigator (PI), Debby manages a team of thirteen including postdocs, PhD students, technicians and undergraduates. With microscopy, genomics and a fair bit of intuition Debby and her team have made some pretty exciting discoveries…

What do you do in the lab?

Our lab looks at brain development. The main way we do this is with model organisms like mice that are well suited to study. We can’t directly study brain development in humans, but mice have a lot of similarities to us in terms of brain development, order of events, cell types and molecules. We use various approaches to manipulate genes of interest and to ask how they can perturb development. Then we use microscopy to get images of those cellular processes. We also take advantage of the ability to generate human cells that are akin to early stages. Basically we use a dual approach to better understand basic processes of brain development. 

Debbie Silver

How do you keep everyone organized?

I meet with everyone weekly to make sure they get at least an hour of my dedicated time. We also have a lab meeting once a week where everyone can share ideas. We store our data on the Duke server and I have everyone keep online LabArchives notebooks. I used to get frustrated looking back at my own paper notebooks, so online notebooks allow us to maintain, backup and share data online to make it easy.

The Silver Lab uses a multidisciplinary approach (including evolutionary genomics, mouse genetics and embryology) to uncover the genetic changes that underlie human-specific brain development and function.

What are some of the processes of brain development you’re trying to understand?

Most recently we’ve been looking at how stem cells divide to make neurons. When I started the lab we were investigating a gene that we knew was important to brain size but weren’t sure how. With that I kind of just followed my nose, if you will, and we found that it was a gene that regulates how cells divide. We designed this crazy experiment where we could control the length of time it took for these cells to divide. In the end when it took longer for the cells to divide they made the wrong number of neurons. This was a really exciting finding. It reminded us to keep our eyes open to what we might find. Another project along these lines looks at asymmetry in gene expression. We looked at a cell that was very elongated and asked if the RNA was sequestered to one side would it impact the cell’s function? We wanted to know about RNAs important for stem cells, and we determined that RNA can be transported to far away locations in these cells to control behaviour.

Brain imaging

Has COVID changed how you work?

 Our lab shut down in mid March through June.  I was working from home trying to make sure everyone in the lab was doing ok both in terms of science and mental health, too. I could keep doing my job at home and some of my researchers used this time to write papers and reviews or perform additional data analysis. If we weren’t using online notebooks this would’ve been really hard. Being able to access work from home was key. We’ve slowly ramped back up in lab with shifts now. We’re using Scheduler to manage socially distanced work and have moved benches around to create more space.

Have you had any ‘ah-ha’ moments in the lab?

We’ve had a few. Several findings in particular led to papers that I am excited about. When you start your own lab you don’t really know what you’re doing, you have confidence but at the same time you’re asking ‘Will this work out?’ For example, we were trying to understand how human differences in our genome might shape why our brains are the way they are. We looked at mice and saw that when we introduced a genomic change, brains developed differently. This gave me a sense that other systems we’d built were developing in the right direction.

Any takeaways from 2020 so far?

I think the silver lining has certainly been learning how easy it is to use Zoom. I’ve had meetings with people and colleagues from different labs, joint lab meetings across continents and to me that is a cool aspect that is easier than we imagined. The reality is that we can share a lot more info that we appreciated before. The world is smaller than we thought.