About This Project

Ask the Scientists

What is the context of this research?

We want to investigate whether the ability of gamma-synuclein to induce alpha-synuclein aggregation that we observed in vitro plays a role in human brain and may be an important step in the development of various NDDs. As a first step we will use the samples of brain from patients with various NDDs, for example, PD, Alzheimer’s disease with Lewy bodies and dementia with Lewy bodies in order to reveal whether a-synuclein and oxidized g-synuclein are colocalized in parts of the brain where deposits are usually found. For this purpose we will use antibodies to a-synuclein and oxidized g-synuclein.

This research is risky in the sense that it is a hypothesis based on previous research that has been conducted in vitro. If that is successful, we will know at least one mechanism initiating the formation of protein inclusions. Then we will test whether oxidized g-synuclein is able to trigger the formation of aggregates and inclusions of other proteins, such as amyloid beta and Tau (Fig. 2). For this purpose we will use in vitro aggregation assays and cell models.

What is the significance of this project?

If successful, the results obtained will help to understand what initiates the aggregation of proteins causing the formation of toxic inclusions in human brain. Furthermore, this project may provide a new marker, since synucleins are present in cerebrospinal fluid (CSF) and the analysis alpha-synuclein and oxidized gamma-synuclein in CSF may be an important diagnostic tool for early stages of NDDs.

What are the goals of the project?

The total cost for this experiment is $12,000. On the first step the experiments with immuno- fluorescence will be conducted in our laboratory in collaboration with the Department of Pathology, Kansas University Medical Center. The brain slices from patients with Parkinson’s disease, Alzheimer’s disease with Lewy bodies and dementia with Lewy bodies are available in this department. We will need to purchase antibody to alpha-synuclein and gamma-synuclein as well as reagents for sample fixation and preparation for microscopy. On the second step we will conduct experiments in vitro in order to reveal whether gamma-synuclein initiate aggregation of other naturally unfolded proteins, for example beta-amyloid and Tau. For these experiments we will need to purchase commercially available recombinant proteins.

An exciting aspect of this project is the ability for me to conduct an interesting research outside the traditional research system. This is only possible because of the recent development of Microryza and Science Exchange. Microryza will allow me to raise the funding required to conduct the project, and Science Exchange provides me with access to an expert scientist to conduct the lab experiments required. It is exciting to think of the potential for all kinds of people to begin to conduct research projects using a strategy like this.