Contribute to exciting research on axon degeneration, a centerpiece of many neurodegenerative diseases, and a subject at the forefront of current neurodegeneration research.
Axons are the longest cellular projections of neurons relaying electrical and biochemical signals in nerves and white-matter tracts of the nervous system. As such, they are critical for neuronal wiring and transport of neuronal maintenance signals. Axons do not exist in isolation, but are inextricably and intimately associated with their enwrapping glia (Schwann cells and oligodendrocytes) to form an unique axon-glia unit.
Because of their incredible length and energetic demand (human neurons can be one meter long), axons are very vulnerable and at continuous risk of damage. Many debilitating neurodegenerative disorders share the common feature of early damage and demise of axons. The most relevant neurological symptoms in a number of these conditions are due to compromised axon integrity. Thus, neuroprotective therapies promoting axon stability have great potential for more efficient treatment.
The identification of such therapies requires a better understanding of the mechanisms underlying axon degeneration. Our laboratory is investigating the cell-autonomous and non-cell-autonomous mechanisms of the degeneration of axons. In other words, we are attempting to elucidate what causes axon breakdown from within neurons, and which external (glial) events trigger axon loss.
Recent studies indicate that axonal degeneration is an active and highly regulated process akin to programmed cell death and occurs secondary to bioenergetic failure. Moreover, it is increasingly realized that axonal maintenance relies not only on neuron-derived provisions but also on trophic support from their enwrapping glia. The mechanism for this non-cell-autonomous support function remain unknown, but emerging evidence indicates that it is distinct form the conventional glial role to insulate axons with myelin. We are pursuing the intriguing question whether abolished support by aberrant delivery of metabolites and other trophic factors from glia into axons is mechanistically linked to the induction of axonal auto-destruction. This concept is supported by our recent findings indicating that Schwann cells shuttle glycolytic energy substrates into distressed axons, and disruption of this metabolic support function in glia promotes axon demise.
Our studies are sponsored by federal agencies (NIH NINDS) as well as private foundations (Muscular Dystrophy Association USA).
Key lab publications in regards to the topic:
The specific outcomes of this project will be identified by the faculty mentor at the beginning of your collaboration. Possible tangible project outcomes include, but are not limited to
|Length of commitment||To be determined by student/mentor|
|Level of collaboration||To be determined by student/mentor|
|Benefits||Academic Credit, Stipend, Volunteer, Work Study, depending on commitment|
|Who is eligible||Anyone with a genuine interest in neurodegeneration/neuroscience research, and motivated to be actively involved in the above-described project.|
If you are planning to use this project to satisfy program requirements for your academic major or minor, it is your responsibility to obtain approval from your academic department prior to beginning the project.
The specific preparation activities for this project will be customized through discussions between you and your project mentor. Please be sure to ask them for the instructions to complete the required preparation activities.