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Interneuron Development in the Zebrafish Spinal Cord

  • Full or part time
  • Application Deadline
    Thursday, December 15, 2016
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The Lewis Lab recently moved to Syracuse University from Cambridge University in the UK. We use Genetics, Cell Biology and Developmental Biology to investigate how the correct number and pattern of interneurons forms in the vertebrate spinal cord, and how these interneurons acquire their specific characteristics and functions.

The vertebrate nervous system contains many different specialized neurons that form at characteristic positions and develop specific axonal connections and functions. Most of these neurons are interneurons, but we currently know very little about how different types of interneurons are specified.

We primarily use zebrafish embryos as a model system, as the embryos develop outside the mother and are transparent and their relatively simple nervous system facilitates studies of neuronal circuitry and function. We use transgenic lines of zebrafish in which neurons express Green Fluorescent protein to study these cells in live and fixed embryos. As most of the genes involved in spinal cord development are conserved between vertebrates, the insights that we gain about the functions of specific genes should be widely applicable.

A PhD project is available to investigate the roles of specific regulatory genes in determining different neuronal characteristics in the zebrafish spinal cord.

Experiments included in this project may include:

1. Investigating the functions of particular regulatory genes in interneuron specification by ectopically expressing mRNAs and/or knocking down gene function using mutants, or antisense oligonucleotides called morpholinos, and examining the effects on molecular markers and interneuron characteristics such as morphology and neurotransmitter expression.

2. Observing the development and morphology of specific interneurons using confocal microscopy.

3. Determining which regulatory genes are expressed by particular interneurons using in situ hybridisation and antibody stainings and/or fluorescent activated cell sorting (FACS) and microarray analysis.

4. Constructing lines of zebrafish in which Green Fluorescent Protein (GFP) is expressed in cells that normally express a particular gene

5. Using calcium indicators such as the genetically encoded calcium indicator Chameleon to monitor the electrical activity of specific neurons in wild-type and experimental embryos during particular behaviours.

See http://lewislab.syr.edu/research.html for more information about our research.


Application Deadline: Until December 15th 2016, we will be accepting applications for a start date of end of August 2017. After this we will be starting to accept applications for a start date of end of August 2018.

If you are interested in applying please can you first fill in the preapplication at http://biology.syr.edu/grad/pre_app.htm


Syracuse has its own airport (15 minute drive from downtown) and is close to Toronto, New York City, Philadelphia, Montreal as well as the natural beauty of Upstate New York (Niagara Falls, The Finger Lakes, Adirondack lakes and mountains).

Syracuse University shares a campus with SUNY Upstate Medical University that has active research programs in Cell and Developmental Biology and Neuroscience http://www.upstate.edu/research/research_dept.php and the Lewis Lab are also part of their graduate program in Neuroscience.

Funding Notes

Funding is guaranteed for 5 years. Deadline is December 15th but late applications may be considered.
Funding is a mixture of teaching and research assistantships. Students rotate in 3 labs in first year and then choose one for PhD. Other Developmental Biology and Neuroscience labs at Syracuse University include:

Sarah Hall View Website
Melissa E. Pepling View Website
Eleanor Maine View Website.
Sandra Hewitt View Website
James Hewitt View Website
Jessica McDonald View Website

For a full list of faculty see View Website

For more details on graduate program see View Website

There is a preapplication that should be filled in online first. See View Website

References

K. E. Lewis (2006) How do genes regulate simple behaviours? Understanding how different neurons in the vertebrate spinal cord are genetically specified. Philosophical Transactions of the Royal Society B: Biological Sciences 361(1465): 45-66.

William C Hilinski; Johnathan R Bostrom; Samantha J England; José L Juárez-Morales; Sarah de Jager; Olivier Armant; Jessica Legradi; Uwe Strähle; Brian A Link; Katharine E Lewis (2016) Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons. Neural Development 11:16 DOI: 10.1186/s13064-016-0070-1

J. L. Juarez-Morales, C. Schulte, S. A. Pezoa, G. K. Vallejo, W. Hilinski, S. England, S. de Jager and K. E. Lewis (2016) Evx1 and Evx2 specify excitatory neurotransmitter fates and suppress inhibitory fates through a Pax2 independent mechanism. Neural Development. 11: 5 DOI:  10.1186/s13064-016-0059-9

S. England, M. F. Batista, J. K. Mich, J. K. Chen and K. E. Lewis (2011) Roles of Hedgehog Pathway Components and Retinoic Acid Signalling in Specifying Zebrafish Ventral Spinal Cord Neurons. Development 138: 5121-5134.

D. K. Goode, H. A. Callaway, G. Cerda, K. E. Lewis and G. Elgar (2011) Minor change, major difference: divergent functions of highly conserved cis-regulatory elements subsequent to whole genome duplication events. Development 138: 879-884.

C. J. Schulte, C. Allen, S. England, J. Juárez-Morales and K. E. Lewis (2011) Evx1 is required for joint formation in zebrafish fin dermoskeleton. Developmental Dynamics 240: 1240-1248.

K. Wotton, F. Weierud J. L. Juarez Morales, L. E. Alvares, S. Dietrich, K. E Lewis (2010) Conservation of gene linkage in dispersed vertebrate NK homeobox clusters. Development, Genes and Evolution 219:481-496

G. Cerda, M. Hargrave, K. E. Lewis (2009) RNA profiling of FAC-sorted neurons from the developing zebrafish spinal cord. Developmental Dynamics 238: 150-162.

M. F. Batista and K. E. Lewis (2008) Pax2/8 act redundantly to specify glycinergic and GABAergic fates of multiple spinal interneurons. Developmental Biology 323: 88–97.

M. F. Batista, J. Jacobstein and K. E. Lewis (2008) Zebrafish V2 cells develop into excitatory CiD and Notch signaling dependent inhibitory VeLD interneurons. Developmental Biology 322: 263-275.

K. Wotton, F. Weierud, S.Dietrich, and K. E. Lewis (2008) Comparative genomics of Lbx loci reveals conservation of identical Lbx ohnologs in bony vertebrates. BMC Evolutionary Biology 8:171.


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