Research Group of Dr Michael Barresi, Smith College, Northampton, MA

Research Group of Dr Michael Barresi, Smith College, Northampton, MA

Barresi lab (from left to right): Alexander Workman (technician), Azucena Ramos (undergraduate), Sean Burton (Ph.D. student), Elizabeth Deshene (undergraduate), Kimberly Johnson (Masters student), Michael Barresi (PI), Sarah Bashirrudin (undergraduate).

Dr. Michael Barresi is an assistant professor in the department of Biological Science at Smith College, Northampton, MA. Research in the Barresi lab is focused on how glial cells help wire the nervous system in the embryonic zebrafish brain. They discovered that astroglial cells provide a substrate for midline crossing axons in the forebrain. They are hoping to determine how the cellular identity of these astroglial cells is established, what molecular cues control glial cell positioning in the brain, and how these astroglial cells actively participate in axon guidance. Understanding how the process of axon guidance is normally regulated during embryonic development will provide key insights into the creation of potential therapies for spinal cord injury and neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and Multiple Sclerosis.

In 1997, Michael obtained his B.A. in Biology from Merrimack College in North Andover, MA, where he also minored in Studio Art. In 2001, Michael received his Doctoral degree in Developmental Biology from Wesleyan University in Middletown, CT, where he studied under the supervision of Dr. Stephen Devoto. His research here was focused on investigating the requirement of Sonic Hedgehog signaling for slow muscle fiber type development during zebrafish embryogenesis and muscle growth. 

Prior to his invitation to Smith College, Michael completed a three year postdoctoral fellowship in Dr. Rolf Karlstrom’s lab at the University of Massachusetts, Amherst, and it was here that he first became immersed in the field of neuroscience. The Karlstrom lab studies brain patterning with a particular emphasis on pituitary specification as well as optic chiasm and commissure formation in the forebrain.  Using different imaging techniques in combination with genetics and gene-knock-down approaches, they investigate the formation of nerve pathways during embryonic development. Michael’s postdoctoral research was focused on analyzing the role of Slit signaling on the positioning of forebrain commissural axons and astroglial cells in the zebrafish (Movies made by Michael using Volocity Visualization, during his time in the Karlstrom lab).

In 2005 he joined the faculty of the department of Biological Sciences at Smith College. In addition to his research, Michael uses his artistic abilities to illustrate some of the seemingly abstract biological processes that he researches.

The Barresi lab is currently investigating the roles of the Slit and Robo gene families during axon and glial cell interactions using the zebrafish as a model system.  Michael says "One of the reasons we use the zebrafish model system to study brain development is the fact that zebrafish embryos are remarkably transparent, enabling all types of microscopy particularly fluorescent microscopy of both fixed and live cells in vivo".

Barresi lab projects include:

  1. Glial Cell Fate - They are interested in defining the cellular identity of astroglial cells in the forebrain. By using both gene and cell markers they are attempting to determine exactly what types of glial cells exist in the forebrain during embryonic and larval development. In addition, the fate of each cell type is precisely regulated by the signaling systems present in their environment. They are using a series of zebrafish mutants that affect the Hedgehog and Fibroblast Growth Factor signaling pathways to determine if either of these signaling systems plays a role in glial cell differentiation.
  2. Glial Cell Guidance - They have shown that the Slit family of axon guidance repellents may play a role in determining the position of astroglia in the forebrain. By using specific knock-down techniques they are testing which slit genes and their receptors are required for glial cell guidance in the forebrain.
  3. Axon - Glial Interactions - In order to investigate the behaviors of two cells interacting, you need to be able to watch those cells in their normal context. The Barresi lab has been developing tools to watch both glial cells and axons in the live embryo as they contact each other during the formation of the first neural pathways. More specifically, they are generating transgenic fish lines that drive the expression of Red Fluorescent Protein specifically in glial cells and Green Fluorescent Protein in axons. These fluorescent lines will allow them to conduct time-lapse microscopy to watch the behavior of labeled cells at different times.

The movie shows a view of the zebrafish forebrain at 30 h. Images were acquired using a laser scanning confocal microscope. The movie was made using the 3D rendering features of Volocity Visualization. The z stack projection was rotated around the Y axis. Labeled antibodies against acetylated tubulin (red) were used to label all axons in the forebrain. The anterior and postoptic commissures can be seen. Cells from the animal cap of a gastrula staged gfap:gfp transgenic embryo were transplanted into a non-GFP transgenic line.  The green cells seen in the movie are the surviving transplanted cells that took root in the forebrain. Appropriately, these cells generated a radial glial morphology. Using Volocity, Michael and his colleagues were able to see, for the first time, clear cellular morphologies. By using the interactive features of Volocity Visualization, they were also able to observe cell-cell interactions from different perspectives.   

Michael says "Whilst I was a postdoctoral fellow in Rolf Karlstrom's laboratory, I utilized Improvision's Volocity software to 3D reconstruct the ventral forebrain of zebrafish embryos. The software allowed us to fly though the brain to look at the labeled axons and glial cells, and to see how they interacted from multiple angles. This 3D approach actually changed many previous hypotheses about the positioning of these cell types and cell parts during commissure formation. We saw things in a new light through this software, and we are now able to generate more accurate hypotheses and experiments. In my own lab at Smith College we are just beginning to take the next step toward understanding the behavioral interactions that axons and glial cells exhibit together during the wiring of the brain.  To do this we will be conducting long-term laser scanning confocal microscopy of live zebrafish embryos, imaging both neurons and astroglial cells in the forebrain.  Again, with the use of Volocity, we will be able to analyze these now 4D data sets in a new light: looking at the process from multiple angles and more importantly quantifying many parameters of the behaviors".

Please visit the Barresi lab to learn more about Michael’s research and to watch more movies made using Volocity Visualization.