Section: Research

Postdoctoral Position Available

Michael Francis, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Neurobiology

Joint Faculty In:
   Program in Neuroscience

Synaptic transmission and C. elegans locomotion                          

Fast synaptic transmission underlies the vast majority of cell-cell signaling in the nervous system.  Alterations in synaptic properties can have profound effects on the output of a neural circuit.  What genes regulate synaptic properties and how do changes in circuit properties translate into changes in behavior?

Research in my laboratory explores these general questions in the context of a neural circuit responsible for locomotory behavior in the model organism Caenorhabditis elegans.  C. elegans is a free-living soil nematode that possesses a simple, well-defined nervous system and is amenable to rapid genetic analysis.  Our research pairs genetic and cell biological analyses with recently developed patch-clamp electrophysiological techniques to study the molecular and cellular basis of C. elegans movement.  The neurons responsible for controlling C. elegans movement are well characterized and the basic locomotory control circuit consists of 3 synapses (Figure 1).  Signaling between neurons of this circuit is mediated by a variety of conserved synaptic proteins, including ligand-gated ion channels such as glutamate receptors and nicotinic acetylcholine receptors.  Our work focuses on the following areas:

Synapses at the Neuromuscular Junction

At least 3 distinct subtypes of post-synaptic receptors are expressed in C. elegans body wall muscle: a single subtype of GABA receptor and at least 2 subtypes of ionotropic acetylcholine receptor (AChR). The 2 AChR subtypes present at the neuromuscular junction (NMJ) can be distinguished pharmacologically on the basis of their differential sensitivity to the cholinergic agonists levamisole and nicotine. Recently, we identified the acr-16 gene as encoding an essential component of nicotine-sensitive receptors.  Worms lacking both levamisole receptors and ACR-16 receptors are paralyzed and exhibit a complete loss of excitatory synaptic transmission at the NMJ (Figure 2).  We have found that the Ror receptor tyrosine kinase CAM-1 is selectively required for normal ACR-16 mediated synaptic currents.  We are continuing to study the role of CAM-1 as well as conducting forward genetic screens to identify additional modifiers of cholinergic signaling at the NMJ.  These modifiers may include gene products required for trafficking, localization or function of post-synaptic receptors as well as genes required for neurotransmitter release and we are currently employing a multi-faceted approach including cell biology, microscopy, electrophysiology and genetics to determine the precise functional roles of these modifiers.  We believe that our approach will allow us to identify conserved gene products that regulate cholinergic neurotransmission in C. elegans as well as in the vertebrate nervous system.

Motor Neuron Excitability

In addition to the nAChRs present at the NMJ, a wide variety of nAChR subtypes are also expressed in the nervous system, in particular in motor neurons.  However, little is known about the role of these receptors in regulating motor neuron excitability and how excitation of the motor neurons couples to muscle contraction and ultimately movement.  We have identified several additional acr gene products that are expressed in motor neurons and are currently exploring the role of these AChRs in regulating locomotion. 

We are also taking a forward genetic approach to identify modifiers of synaptic transmission in motor neurons.  The identification of new genes that regulate motor neuron synapses will help provide a more clear mechanistic understanding of synaptic development, post-synaptic receptor localization, ion channel function and the role these receptors play in controlling C. elegans movement.

Office: 715
Phone: 508-856-1496
E-mail: Michael.Francis@umassmed.edu
Keywords: Neurobiology, Organisms - C. elegans, Electrophysiology, Genetics, Synapses

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Francis for additional details.