Dr. Zhang’s Drosophila Lab

Dr. Ping Zhang and his team at of the University of Connecticut have been studying the genetics of neurodegenerative diseases in the model organism Drosophila melanogaster. Fruit flies have genomes that share roughly 60% gene homology with humans, making them an easily comparable species. Dr. Zhang’s laboratory mainly focuses on three diseases: Huntington’s, Parkinson’s, and Amyotrophic Lateral Sclerosis (ALS). All three of these neurodegenerative diseases lead to slow and steady damage to neurons, negatively affecting the patient’s movement.

With years of worldwide studies in the past, scientists have already uncovered many relationships between genes and their roles in corresponding pathways. Dr. Zhang takes our understanding a step further, hoping to “provide important avenues for potential therapeutic remedies.” The overarching objective of his laboratory is to identify important genes that interact with toxic human neurodegenerative disease proteins. To quote Zhang, “our goal is to find the critical players that mediate the toxicity of human neurodegenerative proteins.” With funding mainly from the University of Connecticut, fruit flies with genetically engineered constructs that allow human genes to be expressed can be mostly obtained from colleagues and studied. The diseases are often examined by inducing a mutation to a certain gene and observing the physical effects. Mutated genes are commonly linked with a physical marker, such as eye color or wing shape. This way, the researchers can visually determine if the connected mutant gene is expressed, and to what extent. It is important to note that neuronal genes are expressed in the eyes, making them a valuable organ to work with.

Increasing expression for various genes can provide insight as to which are the most important to regulate in the neurodegenerative pathways. Overexpressing genes involved with these pathways often lead to death, a genetic term coined “synthetic lethality.” For example, this result can be caused from an increased presence of a neuronal toxic protein in the body. Because of neuronal relationship with the eyes, a fly with this phenotype may have deranged eye morphology and completely lack pigment.

Alternately, knock-out or knock-down experiments decrease the amount of gene product. If a regulatory gene cannot properly play its role, the disease may proliferate uncontrollably. Carefully manipulating a fly strain’s genome has provided useful information as to which genes should be moderated in future studies.

To collect data from the genetic manipulations, many molecular technologies are used in this laboratory. Gel electrophoresis uses an electric current to separate DNA fragments based on their size or number of base pairs. It can also provide evidence as to which genes are either present or missing in a fly strain’s genome. PCR, or polymerase chain reactions exponentially increase the quantity of specific DNA samples. The physical DNA can be tested with methods such as gel electrophoresis or to be run on a genomic sequencer. Genome-wide interactions are examined to see if manipulating one gene can have effects in another chromosome or chemical pathway. RNA sequencing, or RNA-seq, via “next generation sequencing” is also performed in this lab. This approach can determine the quantity of gene transcription products, which can vary in different parts of the body, fly strains, or time in the life cycle.

Since the year 2000, the complete Drosophila genome has been fully sequenced. Knowledge of genetic engineering has spread rapidly across the globe, and scientists have been working together to make genetics an easier field to understand. Openly accessible databases such as FlyBase make Drosophila genetics easier to work with and symbolize the future and power in working with shared knowledge. As a young, motivated scientist, I am eager to discover how new genetic technologies can deepen our understanding for molecular and chemical systems.