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Tools of the Trade: Q&A with Luke Lavis

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05/31/18 | Tools of the Trade: Q&A with Luke Lavis

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Tool-building has always been an essential part of scientific progress and a core part of the research at Janelia Research Campus. With the recent changes in its focus areas, how is Janelia staying committed to tool-building?

 

Q:

In your own words, what is Molecular Tools and Imaging?

A:

Molecular Tools and Imaging refers to Janelia’s tool-building efforts to develop reagents and instrumentation that push biological investigation forward. In Janelia’s first decade, this involved the focused development of fluorescence microscope technology, including the design of new microscopes and the development of new fluorescent sensors and labels. Moving forward, this group will evolve and expand to include different molecular tools and imaging modalities to synergize with the new research areas that will come to Janelia.

   

Q:

Janelia recently announced changes to its research structure. How does Molecular Tools and Imaging fit into this model? Why is this an important focus area?

A:

Janelia was founded on the idea that tool-builders should work alongside biologists to solve important scientific problems. The change in research structure reaffirms the importance of this type of science. One of Janelia’s explicit mandates is to do research that is typically not prioritized by other funding agencies. Making tool-building equivalent in significance and scale to our biological programs is unique in the scientific landscape.

   

Q:

What have you already accomplished in this focus area?

A:

Janelia has been remarkably successful in this area. We’ve made tremendous strides in developing techniques that enable scientists to view cellular processes at work even in intact animals. Our reagents and other tools are used by thousands of labs around the world, and researchers are either replicating our microscopes or using them through the Advanced Imaging Center.

Some examples of notable projects include:

   

Q:

In addition to leading Molecular Tools and Imaging, you’re also managing your lab. How do these two different roles inform each other?

A:

My job is to lead by example and try to walk a fine line between running an innovative research program in chemistry, my chosen field, and supporting the overall tool-building efforts at Janelia. Chemistry is the “central science,” and chemists are used to interfacing with other disciplines like physics, biochemistry, and biology. It is a natural fit to interact with the broader Janelia community as both the head of Molecular Tools and Imaging and as a group leader.

   

Q:

In your lab, what work are you most proud of so far?

A:

The environment at Janelia allows the time, resources, and freedom to pursue problems that can be off the beaten path of science. Early on, we invested some effort in reinventing the century-old field of small-molecule fluorophore synthesis. We used this new chemistry, some physical organic chemistry principles, and a bit of imagination to discover a simple and straightforward method for improving the properties of fluorophores across the visible spectrum to create the Janelia Fluor dyes. But I am even prouder of our efforts to disseminate these fluorophores broadly to nonprofit researchers around the globe. Janelia’s commitment to providing open-source scientific tools free of charge and without restrictions is driving science forward and fostering a renewed interest in chemical tools for biology.

   

Q:

What are some upcoming projects (or ongoing research) you are excited about?

A:

I am particularly excited about a new class of hybrid indicators that combine the excellent brightness of synthetic small-molecule fluorophores, like the Janelia Fluor dyes, with the specificity of genetically encoded fluorescent proteins, like GCaMP. Developing these hybrid indicators is a collaborative effort among my lab, Eric Schreiter’s lab, and our biology partners, Misha Ahrens and Karel Svoboda. We have been able to create new functional indicators that have superior qualities to genetically encoded indicator systems for things like voltage or calcium to literally light up active neurons.

   

Q:

Is Molecular Tools and Imaging self-driven or driven by other science in the building?

A:

It’s both. Over the last decade, we have learned to solve this dilemma by supporting tool-builders who are independent experts in their own fields and who have research programs that are moving in generally useful directions for biology. Some tool-builders have their own biological questions, some collaborate, but Janelia’s patient backing of basic research in the physical sciences is key to our success.

   

Q:

What kinds of people do you think will excel in this new environment at Janelia?

A:

When I applied to work at Janelia, one of the things that resonated with me was an interview with Janelia’s executive director, Gerry Rubin, who stated that Janelia was looking for “misfits,” scientists who wanted to do academic science but didn’t fit into the standard academic environment. Part of my job now is to identify the next generation of scientists who will think outside the box and create the reagents and hardware that will break through barriers that limit biological discovery. The arrival of different research foci is exciting, since it will give tool-builders new biological research problems to solve.

   

Q:

What would you say to someone who is interested in coming to Janelia?

A:

Janelia is the place where you can do your dream experiment. So much of science in the current funding climate necessitates trying to figure out how to relate your research interests to human health; this is especially challenging for tool-builders. At Janelia, you can spend time doing the science that gets you up in the morning without worrying about coming up with the right research question to get funding. For me, Janelia’s initial focus on neuroscience and high-end imaging proved to be an ideal challenge for chemical tools. We failed more than we succeeded, but we internalized the Janelia ethos – utility over novelty – and slowly made some progress. These hard-won lessons are essential to pass on to the next generation of tool-builders and tool-users.