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Markita Landry aims to advance the frontiers of neuroscience and psychiatry with dopamine nanosensors

By February 15, 2018April 23rd, 2018No Comments

Infrared fluorescence microscopy and nanosensors can enable imaging of brain neuro-chemistry.

Markita Landry, Helen Wills Neuroscience Institute faculty member and Chan Zuckerberg Biohub Investigator, was selected as a 2018 Sloan Research Fellow in Neuroscience for her research developing tools to study brain chemistry.

“This is an exciting time to extend the boundaries of neuroscience into adjacent fields,” Marla Feller, Professor and Head of Neurobiology at UC Berkeley, wrote in a statement about Landry’s award. “The tools the Landry Lab are developing could provide new abilities to study neuromodulation. Her goal of imaging neuromodulation deep in the awake and behaving rodent brain is bold, but she is a fearless researcher. Dr. Landry is among the very best young researchers who is pushing the boundaries of chemistry and physics into neuroscience, and as such, an outstanding choice for a Sloan award.”

Landry is Assistant Professor of Chemical and Biomolecular Engineering, where she engineers nanosensors to image molecules in biological samples. She has identified neuroscience as a field particularly in need of improved sensors to visualize the molecular players.

Neurons in the brain signal to each other by releasing neurochemicals, including neuromodulators. Until recently, there was no way to observe the release and spread of neuromodulators in the living brain. Landry is among the pioneers who are creating novel approaches to directly observe the dynamics of neuromodulators in the brain.

Landry’s approach is to design fluorescent nanosensors for the neuromodulator dopamine. In parallel, she is designing a modified 2-photon microscope for dual-infrared imaging of her dopamine sensors through the skull and deep into the brain tissue of living, behaving animals.

Drugs that interfere with dopamine have been used for over 60 years to treat a variety of psychiatric disorders. Yet the assessment for drug efficacy remains qualitative, consisting of questionnaires and behavioral observations. Landry’s dopamine nanosensors could be used to quantitatively assess how psychiatric drugs affect the release and concentration of dopamine in the brain over time.

“Together with our collaborators in cellular neuroscience, we seek to advance the frontiers of neuroscience and psychiatry in concert with each other.” Markita Landry

Initially, dopamine nanosensors will be a valuable tool for studying the underlying mechanisms of psychiatric disorders. Then, they will be useful as a diagnostic tool to detect psychiatric disorders and determine the appropriate treatment. If successful, Landry plans to extend this approach to the other key molecular players in psychiatric disease – serotonin and epinephrine.

In the Q&A below, Landry tells us how she became interested in visualizing neuromodulators in the brain.

Georgeann Sack: I see that your work is broadly applicable to the biological study of both plants and animals. What makes the tools you are developing particularly well-suited to neuroscience?

Markita Landry: I am a single-molecule physicist by training, having developed instruments for detection of piconewton-scale forces, and nanometer-scale fluorescence localization for my doctoral work. In transitioning to my postdoctoral position, my goal was to leverage my expertise in fluorescence imaging and molecular biophysics to design synthetic molecular imaging tools. As such, my Ph.D. work inspired my postdoctoral work in engineering molecular recognition methods to image molecules in biological samples.

However, a common pitfall in the development of new tools is their implementation in areas where the tool is either redundant or incompatible. In that vein, I have sought to identify outstanding questions that are best addressed by my group’s collective research expertise in molecular imaging. The jump I made from single-molecule biophysics (Ph.D.) to nanotechnology (postdoc) was inspired by the realization that the tools I’d been trained to build and develop could make big advances in another research community.

Today, my research portfolio is motivated by applying the technical strengths of my team in molecular imaging to imaging neuromodulation in the awake and behaving brain. Together with our collaborators in cellular neuroscience, we seek to advance the frontiers of neuroscience and psychiatry in concert with each other.

GS: How will your research improve our understanding of the brain, and why is that important?

ML: To understand and study brain neuromodulation, we must track neurotransmitters deep in the living animal brain on the timescales over which information processing occurs, and also over which disease progresses. My lab focuses on the challenge of imaging key neuromodulators such as dopamine and serotonin. In tandem, we are developing deep-tissue imaging platforms, such as dual infrared 2-photon fluorescence microscopy, to enable in-brain imaging of the probes we develop. I see great potential of these two efforts merged for understanding how neuromodulation may be altered in psychiatric disease.

GS: What previous research has inspired your own?

ML: Ben Barres’ research has been very inspiring in my career. Barres stated that “99% of neuroscientists work on 1% of the interesting questions,” and I find this general outlook to be motivating in choosing what research directions to pursue. I also like to keep this philosophy in mind when coming across unexpected results or even failed experiments – often these negative results prompt questions that could be more interesting to address than the ones I had originally set out to pursue.

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