The “Fly on the Wall” Blog

fruit_fly_drawingBethany Christmann, a Neuroscience Ph.D. student in Leslie Griffith’s lab at Brandeis University has created a blog titled Fly on the Wall. The blog’s purpose is to introduce fly science to a broader audience of non-fly scientists. Check it out if you want to learn more about fly life, current research and how fruit fly research has already made huge contributions to understanding human biology and will continue to do so in the future.

Learn more about research in the Griffith Lab.


Can Self-Referencing Contribute to Memory Errors?

A recent paper in the Journal of Gerontology by Brandeis Ph.D. program alumnus Dr. Nicole Rosa and Professor Angela Gutchess attempts to answer this question. During an interview with ElderBranch, Dr. Nicole Rosa discusses the relationship between self-referencing and false memory. For more information, please read the article on ElderBranch.

Another way that flies sense temperature

If you remember your (bio-)physical chemistry, you’ll remember that most proteins are temperature sensitive. But which ones acts as the sensors that drive behavior in higher organisms? The Garrity Lab at Brandeis has been working on thermosensation in Drosophila, and previous work has implicated the channel protein TRPA1 as a key mediator of temperature preference and thermotaxis,  In a new paper in Nature, members of the Garrity lab working in collaboration with the Griffith and Theobald have have identified another protein, GR28B(D), a member of the family of gustatory receptor proteins, as another behaviorally important temperature sensor, involved in rapid avoidance of high temperatures. Authors on the paper include postdocs Lina Ni (lead author) and Peter Bronk, grad students April Lowell (Mol. Cell Biology) and Vincent Panzano (PhD ’13, Neuroscience), undergraduate Juliette Flam ’12, and technician Elaine Chang ’08.

  • Ni L, Bronk P, Chang EC, Lowell AM, Flam JO, Panzano VC, Theobald DL, Griffith LC, Garrity PA. A gustatory receptor paralogue controls rapid warmth avoidance in Drosophila. Nature. 2013.
  • story at BrandeisNOW


Rectifying electrical synapses in pattern-generating circuits

by Gabrielle Gutierrez

Rectifying electrical synapses are more interesting than they might seem at first. Our recent study finds that they have the potential to allow a circuit to control how robust the circuit output is to modulation of synaptic strength.

Gap junctions allow neurons to communicate quickly by serving as a direct conduit of electrical signals. Non-rectifying gap junctions probably come to mind first for most neuroscientists when they think about electrical synapses, since they are the idealized textbook variety. The electrical current that passes through the non-rectifying type of gap junction is simply a function of the voltage difference between the coupled neurons. However, this is only the case when the two hemi-channels that form a gap junction pore have the same voltage-dependencies.

Schematic shows that neurons can express diverse gap junction subunits (top left). Rectifying gap junction conductance is a function voltage difference between two neurons (top right). Bottom panel illustrates how coupled neuron output depends on the polarity of the rectifying electrical synapse and the intrinsic properties of the coupled neurons.

Schematic shows that neurons can express diverse gap junction subunits (top left). Rectifying gap junction conductance is a function voltage difference between two neurons (top right). Bottom panel illustrates how coupled neuron output depends on the polarity of the rectifying electrical synapse and the intrinsic properties of the coupled neurons.

We know from past electrophysiology studies that a single neuron can express a diverse set of gap junction hemi-channels, enabling it to form similarly diverse gap junction channels with another neuron. This could result in rectifying electrical synapses in which current flows asymmetrically between neurons so that current flow can either be permitted or restricted depending on whether the current is positive or negative. What we didn’t know were the consequences of electrical synapse rectification for a pattern-generating circuit of competing oscillators. Our recently published study in J. Neuroscience addressed this question and led us to conclude that rectifying electrical synapses can change how a neuronal circuit responds to modulation of its synapses – including its chemical synapses. Although we used a computational model for our study, our results indicate that rectifying electrical synapses in biological networks can be an important component in neuronal circuits that produce rhythmic patterns, such as those found in motor systems.

Gabrielle Gutierrez obtained her PhD in Neuroscience from Brandeis earlier this year, and is currently doing a postdoc with Sophie Deneuve at the Ecole Normale Superieure in Paris

Gutierrez GJ, Marder E. Rectifying electrical synapses can affect the influence of synaptic modulation on output pattern robustness. J Neurosci. 2013;33(32):13238-48.

Some papers from July

Between vacation and some busy weeks at work, we didn’t get much of a chance to post stuff about new science from Brandeis. To make up for it, some stuff that we noticed in July:

Relocating the active-site lysine in rhodopsin [...]: Biochemistry grad student Erin Devine uses site-directed mutagenesis to answer questions about convergent evolution. (Oprian and Theobald labs)

[...] nef2 links the Drosophila core clock to fas2, neuronal morphology, and circadian behavior [...]: Postdoc Anna Sivachenko et al. look at the links between the circadian clock and activity-dependent neuronal remodeling (Rosbash lab)

The insulin receptor cellular IRES confers resistance to eIF4A inhibition: MCB grad students Calla Olson, Marissan Donovan, and Mike Spellberg look at how translation of the insulin receptors is controlled during times of stress. (Marr lab) [story at BrandeisNOW]

Fluctuations in shear-jammed states [...] Dapeng Bi (Physics PhD ’12) and coworkers take a stat mech approach to dense granular materials (Chakraborty group)


Sloan-Swartz Computational Neuroscience Meeting July 26-28

sloan-swartz-illustThe annual summer meeting of Sloan-Swartz Centers for Computational Neuroscience will be held at Brandeis this weekend (July 26-28). Neuroscientists from centers at 11 major US educational institutions will convene to talk about research progress from the last year. Talks by professors, postdocs, and grad students will be held Friday through Sunday in the Shapiro Campus Center Auditorium – the schedule is online. The poster session, including posters from Brandeis undergraduates and grad students, will be held on Friday evening. All welcome to attend talks. Food available for those who have preregistered.

A facilitated diffusion confusion dissolution

To udirectbindfd1tilize the information contained within a cell’s genes, the enzyme RNA polymerase must find the beginning of each gene (the promoter).  Finding the beginning is a prodigious task:  RNAP must start at a particular base pair of DNA, but the cell contains millions of base pairs to choose from.  It has been proposed that gene-finding challenge is aided by a process termed ‘facilitated diffusion (FD).  In FD, RNA polymerase first binds to a random position on DNA and then slides along the DNA like a bead on a string until it encounters the target DNA sequence.

single-mol-testIn a recently published study in PNAS (1), biophysicists Larry Friedman and Jeffrey Mumm worked with Prof. Jeff Gelles in the Brandeis Biochemistry department to test key predictions of the FD model.  They used a novel light microscope that Friedman and colleagues invented and built at Brandeis, a microscope that can directly observe the binding of an individual RNA polymerase to a single DNA.  The scientists studied the σ54 RNA polymerase holoenzyme, an RNA polymerase found in most species of bacteria.  Surprisingly, none of the three predictions of the FD model that the experiments tested were found to be valid, demonstrating that target finding by the polymerase is not accelerated by sliding along DNA.  Friedman and colleagues instead propose that RNA polymerases are present in such large numbers that they can diffuse through the cell and efficiently bind to their target sites directly.  The absence of FD may explain how other proteins can bind to positions on the DNA that flank gene start sites and yet not interfere with RNA polymerase finding the gene.

Is this the end of the story? Not likely, given previous publications suggesting FD plays a role for some other DNA binding proteins. Using single-molecule techniques like those developed in the Gelles lab, scientists in next few years should give us a better idea if FD is very rare or very common. [editor: as a chemical engineer, I'm sad to see FD not have a role -- it seemed like such a nice theory...]

Friedman LJ, Mumm JP, Gelles J. RNA polymerase approaches its promoter without long-range sliding along DNA.  Proc Natl Acad Sci U S A. 2013 May 29. [Epub ahead of print]



Making new synapses with Sema4D

There are two main types of synaptic connections in the mammalian brain: excitatory glutamatergic synapses and inhibitory GABAergic synapses. The balance between excitatory and inhibitory inputs a neuron receives regulates the overall activity of neuronal networks; disruptions to this balance can cause epilepsy.

A new paper in J. Neuroscience from the Paradis lab shows that treatment of cultured neurons with the extracellular domain of the protein Sema4D causes a rapid increase (i.e. within 30 minutes) in the density of functional GABAergic synapses. Further, addition of Sema4D to neurons drives GABAergic synapse formation through a previously unappreciated mechanism: the splitting of pre-existing assemblies of the Gephyrin scaffolding protein. To our knowledge this is the fastest demonstration of synapse formation reported thus far and has significant implications for our understanding of the mechanisms of GABAergic synapse formation.

Screen Shot 2013-05-26 at 5.03.05 PMWhile the underlying mechanism of epileptogenesis is largely unknown, recurrent seizures emerge when there is an increase in network activity. One possible therapeutic treatment would be to restore normal network activity by increasing network inhibition. In an in vitro model of epilepsy, acute treatment with the protein Sema4D rapidly silences neuronal hyperexcitability, suggesting a possible use of Sema4D as a disease-modifying treatment for epilepsy.

Lead authors on the paper were Marissa Kuzirian, a grad student in the Neuroscience Ph.D. program, and Anna Moore, a Brandeis Neuroscience postdoctoral fellow.

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