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zebrafish

Above: Different stages of Zebrafish Development (Top, left) A 90 minutes old Zebrafish embryo; (Top, right) A two day old Zebrafish embryo/fry; (Bottom)

interneurons

Above: Individal interneurons in the zebrafish spinal chord labelled with GFP.

spinal interneurons

Above: Spinal interneurons can be individually identified in zebrafish embryos and larvae. This schematic shows the cell body positions and axon trajectories of the major classes of zebrafish spinal interneurons and two of the three major spinal axon tracts (VLF and DLF). Taken from Lewis and Eisen (2003). Dashed lines indicate contralateral axons.

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Above: VeLD and KA interneurons express gata3, scl and GABAergic markers. Lateral views of spinal cord showing VeLD (A & B) and KA (B & C) neurons labelled in green (anti-GFP staining on Tg (8.1kGata1:eGFP) fish). Red staining shows gata3 expression (A); scl expression (B) and expression of GABAergic markers (C).

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Above: Different regulatory genes (transcription factors) are expressed by distinct populations of interneurons in the zebrafish spinal cord. This picture shows lateral and cross-section views of the zebrafish spinal cord at about 18 hours of development. Dorsal is to the top and Anterior to the left. The amniote orthologues of the zebrafish genes are indicated in parenthesis.

Quicktime Movie: timelapse movie of early zebrafish development (1.1MB)

Useful links:

ZFIN (www.zfin.org) the zebrafish database

• Lewis Lab Syracuse ZFIN page

     
 

Research

 

Katharine (Kate) Lewis

Associate Professor


Office: LSC 262
Phone: 315-443-5902
Lab: 315-443-7253

kelewi02@syr.edu

 

Recent News

Biologist Awarded Prestigious Research Grant
April 10, 2014
To say the competition for the 2014 International Human Frontier Science Program Organization (HFSPO) Research Grants was fierce would be a massive understatement. In fact, when the process began more than a year ago, 844 letters of intent were submitted from researchers all over the world. Applicants went through a rigorous year-long selection process and when all was said and done, only 34 submissions were selected to receive awards. Ten awards were given to Young Investigator teams, while 24 program grants were handed out. Among this year’s program grant recipients is an intercontinental team, consisting of Katharine Lewis, associate professor of biology in The College of Arts and Sciences; Claire Wyart of The French Brain and Spine Institute; and Aix Marseille University’s Patrick Delmas. Read article.

 

Scientist Is Recipient of $1.6 Million NIH Research Grant
June 20, 2014
Kate Lewis, an associate professor of biology in The College of Arts and Sciences, has added yet another award to her already extensive list of accolades. Lewis, who earlier this year was awarded a research grant by the Human Frontier Science Program Organization, just received a $1.6 million RO1 research grant from the National Institute of Health (NIH). Lewis will use the money to study how particular types of nerve cells, called interneurons, are specified in the spinal cord. Read article.

 

High School Outreach

Science From a Collegiate Perspective
Henninger High School students spend an afternoon as college developmental biology students. The event , hosted by the Department of Biology in SU's College of Arts and Sciences and organized by Katharine Lewis, associate professor of biology. Read article.

 

Research Team

Sam England (Postdoc), José -Luis Juarez Morales (Postdoc), Livia Andrzejczuk (PhD student), Will Hilinski (PhD student), Paul Campbell (undergraduate researcher), Ria Foye-Edwards (undergraduate researcher), Will Fancher (undergraduate researcher), José Marrero Rosado (undergraduate researcher) , Nicole Santos (undergraduate researcher), Grace Vallejo (undergraduate researcher), Jason Zheng (undergraduate researcher).

Zebrafish husbandry team of undergraduate workers

Ria Foye-Edwards, Angela Italia, Tenzin Kusang, Alessandra Newton, Nicole Santos.



Interneuron Development in the Zebrafish Spinal Cord

The vertebrate nervous system contains many different specialized neurons that form at distinct, 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. In recent years we have learnt an amazing amount about motoneuron specification in different vertebrates. The success of these studies suggests that we should be able to analyse interneuron development in a similar manner. This is exciting, as interneurons function in almost all neural circuits and behaviours and defects in specific interneurons have been implicated in a number of neurological disorders including schizophrenia, bipolar disorder and Creutzfeld-Jakob Disease.

We are using 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 evidence so far suggests that the morphology and function of different neurons is determined, at least in part, by the specific regulatory genes that they express. Some genes are probably required for survival or specification of particular neurons, whereas other genes are required for specific aspects of neuronal morphology and function. We are therefore investigating which regulatory genes are expressed by specific interneurons and what the roles of these regulatory genes are in determining different neuronal characteristics.

We use zebrafish as a model system, as their relatively simple nervous system facilitates studies of neural circuitry and function and enables cell fate specification to be studied at the level of both single cells and populations of cells. Zebrafish are also a powerful system for combining genetic and embryological studies as their embryos are readily accessible and optically transparent, allowing us to easily follow the development of individual neurons and observe gene expression in live embryos; and mRNA over-expression methods, mutant lines and antisense oligonucleotide techniques allow us to quickly and easily examine the functions of different proteins in vivo. 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.

The knowledge that we gain from this research will ultimately be important for developing treatments for nervous system diseases, disorders and tumors, as well as methods for facilitating the repair of particular nerves after injury or neurodegeneration. For example, understanding the roles of different genes in specifying particular neurons will enable researchers to grow specific types of neurons from stem cells for treating conditions such as Alzheimer’s disease, Parkinson’s disease, stroke and spinal cord injuries. In addition, understanding the genetic differences between neurons will help us to understand why neurodegenerative diseases often only affect specific classes of neurons.

Our long term goals are to determine not only how different neurons are specified, but also how specific neurons function in particular neural circuits and behaviours. This will enable us to connect how the nervous system develops with how it functions. Zebrafish are ideal for these studies as they are a genetically tractable vertebrate, in which it is possible to follow the development, and test the function, of different neurons in live embryos. For example, we can use transgenic GFP lines to identify specific neurons in live embryos, observe how neurons connect with each other, test the functions of these resulting circuits, and determine how these circuits or functions change when particular genes or neurons are lost. We can also examine existing zebrafish mutations that potentially affect neural development or behaviour, and conduct new mutational screens, to identify additional, and potentially novel, genes that affect neural development and function.

 

PhD and Postdoctoral Research Projects

Funded PhD places are available though the departmental PhD program. Please see the departmental website and fill in the online preapplication form.

Postdoctoral applicants should contact me directly.

Projects are available to investigate which regulatory genes are expressed by specific interneurons and/or the roles of specific regulatory genes in determining particular functional neuronal characteristics. Experiments 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 FAC sorting 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 genetically encoded calcium indicators Chameleon and GCamp to monitor the electrical activity of specific neurons in wild-type and experimental embryos during particular behaviours.

6. Determining the expression patterns of spinal cord genes in other vertebrates such as dogfish (a type of shark) to learn about spinal cord evolution.


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