Project Title: Genetic Modification of Zebrafish to study Hydrocephalus

Faculty Sponsor: Frank Miskevich

Department: Biology



Project Description: Hydrocephalus is the enlargement of brain ventricles that leads to learning defects, gait problems and neuronal loss when left untreated.  A common feature of hydrocephalus is an increase in pressure of the cerebrospinal fluid, the material surrounding and supporting the central nervous system.  Because hydrocephalus involves the complex interaction of many different cells from the nervous and circulatory systems, animal models which mimic the human disease present a powerful mechanism to study the molecular underpinnings in detail.  Previous research has shown that cilia plays a critical role in preventing hydrocephalus, as mutations that disrupt ciliary function or orientation can cause the disease.  The precise role of cilia in the disease has not yet been identified.  This research project will address whether cilia serve a sensory and/or mechanical role in regulating the size of the brain ventricles using high-speed video microscopy and genetic manipulation of zebrafish embryos.  More specifically, fibroblast growth factor, a known causal factor in hydrocephalus, will be tested for its effects on ciliary function and ability to increase cerebrospinal fluid production.  This research will help to define the biochemical mechanisms by which cilia are involved in causing a neurodegenerative disease in humans.

Student Tasks & Responsibilities:  Students will use and develop lab skills to study, manipulate, and piece together pieces of DNA.  These skills form the key building blocks of molecular genetics, a central element of modern biology.

Minimum Student Qualifications:  Students should have completed at least 2 semesters of general chemistry beyond high school level (ie. beyond Chm-140), pre-calc or higher, Principles of biology (Bio-113), and either cell biology (Bio-326) or genetics (bio-328).  Students routinely make solutions, make dilutions, measure microliter amounts, and use techniques such as PCR and/or fluorescence microscopy to build or ananalyze the effects of genetically modified DNA.

Proposed Starting Date: June, 2013

Proposed Ending Date: December, 2013