Research

Our lab develops microtechnology tools to observe in vivo neuronal and behavioral responses to precise stimulation. We study the molecular and genetic basis of neural excitability, how it directs information flow within neural circuits, and its role in neuropsychiatric disorders.

 

We are an interdisciplinary group, combining biomedical and traditional engineering with neuroscience, genetics and optics. tools


Project Areas:

Our projects are focused on understanding how neural excitability is modulated by chemicals, genes, experience (such as learning), and states (such as sleep or starvation).  Some current project realms include the following:

  1. Functional screens for modulators of neural dynamics:

    C. elegans can be used as a model for human disorders related to voltage-gated calcium channels, like epilepsy and autism. To introduce human mutations in the worm, we are using CRISPR-Cas9 and standard genetic techniques, like cloning, transgenics, crosses, PCR and sequencing. When appropriate, we characterize our models by monitoring and quantifying calcium activity (GCaMP) during microfluidic or optogenetic (Chrimson) stimulation. In parallel, we are combining these established techniques with our recently developed automated high-throughput screening methods to discover potential therapeutics that modulate calcium activity in C. elegans neurons. Altogether, we predict that our research will elucidate novel genetic etiology in human diseases and identify potential neuromodulators for secondary screens in vertebrates.bio_ross

  2. Light sheet microscopy for long-term multi-neuronal imaging with chemical and optogenetic stimulation:

    Our lab has developed inverted selective plane illumination microscopy (diSPIM) methods to record high-resolution, isotropic, fluorescent 3-D volumetric images of multiple neurons for long periods of time (>12h). We use new protocols for the embedding and immobilization of small organisms (worm, fly, zebrafish, etc.) as well as cellular constructs and tissue sections (brain slices). We aim to study circuit computation in C. elegans when stimulated with natural sensory stimuli (e.g., chemicals) and with arbitrary optogenetic stimulation within compact and well-defined neural circuits. We use these methods to study neuronal response variability, decision-making, and to identify which neurons respond to novel stimuli.diSPIM

  3. Neural signaling changes across physiological and behavioral states:

    C. elegans neural activity and behavior depend on individual animal state and exposure conditions. Our lab aims to understand how neural signaling in C. elegans varies depending on state differences including starvation, sleep and learning, and how these neural variations lead to behavioral output. We assess the learning capability of C. elegans under various stimulation conditions and genetic perturbations using an automated associative learning paradigm. For example, we study changes in associative learning during development, aging and in neuropsychiatric disorders such as Alzheimer’s disease. Additionally, we study how neural responses change during awake and quiescent (potentially, sleep) states.

 


Technologies

PNAS_imagingOur current microfluidic technologies are able to record single neural responses from 20-40 animals at once, either moving or paralyzed, subjected temporal or spatial  patterns of chemicals, gases, vibration, temperature, light, or combinations of these.  These data have illustrated the reliability of some sensory neural responses and the variability of other interneuron responses give rise to probabilistic behaviors.

We continually develop and refine:

  • hardware systems to image behavior, deliver liquids from multiwell plates
  • automation systems to coordinate microscopy, stimulation, and robotic systems
  • software tools to coordinate multivariate data, track behavior, and track neural activity

 


Funding

We are currently funded by the Burroughs Wellcome Fund, the National Science Foundation, the National Institutes of Health, WPI, and UMASS Medical School.

bwf    nsf4      nih          wpi_umms       

 


Lab News

 

Dan’s sleep preprint is out!

Filed in Uncategorized by on October 4, 2019 0 Comments

Congratulations Dan and co-authors on submitting the sleep paper! Adult C. elegans spontaneously sleep in microfluidic devices (depends on fluid flow, oxygen, hunger, and sensory stimulation), and we asked how neural responses change in sleep and awake states. Read more here: http://biorxiv.org/cgi/content/short/791764v1

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Congratulations, Dr. Kyra Burnett!

Filed in People by on May 1, 2019 0 Comments

Our newest PhD graduate successfully defended her thesis, “High-throughput and High-resolution Functional Imaging Methods to Identify Mechanisms of Variable Neural Excitability in C. elegans“. Congratulations to Dr. Kyra Burnett!  In this dissertation, Kyra explored neural responses to a repeated stimulus whose neural response could change minute-to-minute, or remain consistent, identifying the neurons detecting novel stimuli, […]

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Ross wins Sigma Xi doctoral dissertation award

Filed in Awards, People by on April 25, 2019 0 Comments

Ross wins the 2019 Sigma Xi Outstanding Doctoral Dissertation Award for his PhD dissertation in 2018. This award, established in 1983, is presented for outstanding research by students at the doctoral and master’s levels and is sponsored jointly by the Society of the Sigma Xi and the Committee on Graduate Studies and Research. Congrats, Ross!

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“Rapid and gentle hydrogel encapsulation” selected for First Anniversary Collection

Filed in Uncategorized by on February 15, 2019 0 Comments

“Rapid and gentle hydrogel encapsulation of living organisms enables long-term microscopy over multiple hours”, published in June 2018, has been selected for the Nature Communications Biology first year anniversary collection .

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A C. elegans model for the rare human channelopathy, Timothy syndrome type 1

Filed in Publications by on December 19, 2018 0 Comments

A New Micropublication

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Rapid and gentle hydrogel encapsulation of living organisms enables long-term microscopy over multiple hours

Filed in Publications by on June 25, 2018 0 Comments

New Publication in Nature Communications Biology Kyra Burnett, Eric Edsinger & Dirk R. Albrecht

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Congratulations Ross Lagoy, PhD!

Filed in People, Publications by on April 20, 2018 0 Comments
Congratulations Ross Lagoy, PhD!

Ross Lagoy successful defended his PhD Thesis on April 18, 2018. A portion of the work is reported in the newly published ‘Automated fluid delivery from multiwell plates to microfluidic devices for high-throughput experiments and microscopy‘

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SfN Best Presentation Award- Congratulations Ross!

Filed in Awards by on April 13, 2017 0 Comments

Congratulations to Ross Lagoy for receiving the Best Presentation Award from the Society for Neuroscience (SfN), New England’s recent chapter meeting! The lab is very proud that Ross’s hard work and research was recognized by SfN! Way to go!

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GRIE- Congratulations Dan Lawler!

Filed in Awards by on April 13, 2017 0 Comments

On April 11th, Dan Lawler placed 3rd in the Graduate Research Innovation Exchange (GRIE) poster competition for Life Sciences and Bioengineering! Dan was chosen as a finalist from the original graduate pool of 170 students back on February 3rd. Dan had the opportunity to present again at the finals and took 3rd out of 65 […]

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International summer

Filed in Uncategorized by on July 31, 2016 0 Comments
International summer

Our graduate students have been active internationally this summer! Ross Lagoy presented a talk at the CeNeuro2016 conference in Nagoya, Japan on July 30 about his work towards screening chemicals that restore normal neural dynamics in vivo.  Kyra Burnett is at IMP Vienna visiting the lab of Dr. Manuel Zimmer to learn whole-brain imaging techniques […]

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