Axonal transport and Neurodegenerative disease

drawing of a brain with a neural network of lines and circles.

Seeking students to contribute to research exploring motor-disease protein complexes and their role in intracellular transport, as they relate to disease initiation and the aging process, and the development of neuroprotective treatments.

Project description

Within axons, vital cargoes must be transported over great distances along microtubule tracks to maintain cell viability. In neuronal cells, many proteins function in sending and receiving messages, cell repair, and cell protection. The fundamental question my lab is interested in is whether long distance transport problems are an early precursor in neurodegenerative disease initiation, and if so do problems in transport initiate a "domino effect" that ultimately culminates in degenerative pathogenesis. The aging brain and pathology observed in Alzheimer's disease (AD), Huntington's disease (HD), prion disorders such as Creutzfeld-Jacob disease, Parkinson's disease and frontotemporal dementia, could have common molecular mechanisms. As the human brain ages, neurons may become vulnerable and susceptible to environmental/oxidative damage, leading to chronic nervous system damage. Mutations in the transport motor machinery were found to not only affect transport but could also cause degenerative pathology. Thus transport problems may be a common phenomenon that could propitiate dementia and degeneration.

Understanding the molecular mechanisms underlying neuronal dysfunction is important not only in elucidating the mechanisms of disease initiation and the aging process, but also has long term implications for the development of neuroprotective treatments. The emerging hypothesis from our previous work on two human neurodegenerative diseases is that the transport pathway, which is vital for healthy cells, can be compromised during these devastating diseases. Using genetics, cell biology, biochemical, pharmacological and biophysical analysis combined with an in vivo microscopy technique, future work is focused on understanding the nature of these motor-disease protein complexes and how these complexes affect intracellular transport.

We have two main areas of interest:

  1. Identify molecules that modulate transport phenotypes induced by AD and HD proteins to elucidate what specific complexes/cargoes are being transported by these two motor-disease complexes. 
  2. Test small molecule compounds directed at known pathways to determine if the transport pathway can be useful as a therapeutic target.

Project outcome

The specific outcomes of this project will be identified by the faculty mentor at the beginning of your collaboration. 

Project details

Timing, eligibility and other details
Length of commitment To be determined by student/mentor
Start time Fall, Summer
Level of collaboration To be determined by student/mentor
Benefits Academic Credit, Salary / Stipend, Volunteer, Work Study, salary opportunities depended on funding
Who is eligible Anyone motivated to be involved in scientific discovery and curiosity in the unknown.
Goldwater and the National Science Foundation

Students participating in this project might be interested in and eligible for the Goldwater Scholarship and the National Science Foundation Graduate Research Fellowship. Connect with the Office of Fellowships and Scholarships to learn more.

Project mentor

Shermali Gunawardena

Associate Professor

Biological Sciences

H535 Hochstetter Hall

Phone: (716) 645-4915

Email: sg99@buffalo.edu

Start the project

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Fulfilling Academic Major/Minor Requirements

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. 

Preparation activities

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.