The Babcock Lab is interested in understanding the cellular and molecular mechanisms underlying synaptic dysfunction in neurodegenerative diseases.  Synaptic dysfunction is among the earliest hallmarks in several neurodegenerative diseases, yet very little is known about how this dysfunction occurs and how it relates to later stages of disease progression.  We are using the fruit fly, Drosophila melanogaster, to focus our research on the following areas:

1. How do toxic protein aggregates spread throughout the brain?

While most neurodegenerative diseases involve the accumulation of protein aggregates in particular brain regions, these aggregates can spread throughout the brain over time.  Recent evidence suggests that these aggregates can spread across synapses, the connections between neurons.  By expressing fluorescently-tagged “toxic” proteins in small subsets of neurons in the Drosophila brain, we can monitor the extent of aggregate spreading and identify the key regulators required for this spreading to occur.

2. How do synapses degenerate?

We are also interested in studying the degeneration of synapses directly.  To do this, we are focused on the synapses that motor neurons make with muscles, called NeuroMuscular Junctions (NMJs).  These synapses are particularly useful for examining degeneration because they are easily accessible and amenable to both structural and functional analysis.  Using high-throughput screening methods, our goal is to identify the genes responsible for the maintenance of synapses and determine how the loss of synapses relates to neuronal loss.

3. Why are dopaminergic neurons lost in Parkinson’s Disease?

Most neurodegenerative diseases involve the loss of a particularly vulnerable subset of neurons in the brain.  Why are certain populations of neurons vulnerable to a particular type of disease?  To help understand this, we are studying the loss of dopaminergic neurons, which are the type of neurons that are most prominently affected in Parkinson’s Disease.  By identifying genes regulating the loss of these neurons, we hope to gain a better understanding of how this vulnerability can be overcome.