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Spreading of pathological α-Synuclein through the Peripheral Nervous System
Denmark (IMCC) - Aarhus university, Aarhus
Department of Biomedicine, Ole Worms Allé 3, Building 1171, 420 - 8000 Aarhus C
Type of Research Project
- Basic science
What is the background of the project?
Synucleinopathies are a group of diseases defined by the presence of insoluble amyloidogenic α-synuclein (α- Syn) inclusions that can appear in neurons and glia of the central nervous system (CNS). α-Syn pathology has also been found in the peripheral nervous system (PNS), in particular in the enteric and pelvic plexus, and has been postulated that αS pathology may originate in the nerves of the PNS and spread to the CNS. Based on this hypothesis, in 2014 work from Prof. Benoit Giasson laboratory has shown that hind limb intramuscular (IM) injection close to the sciatic nerve of α-Syn fibrils can induce Lewy pathology in the in the brain and spinal cord of human Ala53Thr (M83) Tg mouse model. Nevertheless, few is known regarding the precise mechanisms underlying neuronal transmission of α-Syn from the PNS to CNS at earlier time points and any insights on the spreading mechanism could eventually open avenues for therapeutical interventions.
What is the aim of the project?
To understand the molecular mechanisms underlying the cell-to-cell propagation of α-Syn from the PNS to the CNS.
What techniques and methods are used?
The project involves several techniques of protein biochemistry. The student will have a learning/observation laboratory period and when suitable he/she will execute the tasks, always under supervision. The first step is to extract the soluble and insoluble protein fractions from tg M83 mice brains and spinal cords. Then, total protein determination of the different fractions will be accessed by bicinchoninic acid assay (BCA). Proteins will be separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS- PAGE) and immunodetected by Western-blot and enzyme-linked immunosorbent assay (ELISA).
What is the role of the student?
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Working under supervision, the student is expected to successfully perform well establish protocols in the lab, including extraction of soluble and insoluble proteins (α-Syn) from transgenic mice tissues (brain and spinal cord), SDS-PAGE, Western-blot and ELISA analysis. Using these biochemical techniques, the student will provide new data on the α-Syn spreading and associated tissue toxicity in vivo.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Participation in Group Meetings and Journal Club. The supervisor will provide literature and the theoretical and methodological background for the experiments.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Familiarity with literature on α-Syn biochemistry and aggregation within the context of in Parkinson’s Disease research. Working in a class I laboratory.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Students in biomedical fields
- Lassen LB; Reimer L; Ferreira N; Betzer C; Jensen PH. Protein Partners of α-Synuclein in Health and Disease. Brain Pathol. 2016. doi: 10.1111/bpa.12374.
- Steiner JA; Quansah E; Brundin P. The concept of alpha-synuclein as a prion-like protein: ten years after. Cell Tissue Res. 2018. doi: 10.1007/s00441- 018-2814-1.
- Sacino AN; Brooks M; Thomas MA; McKinney AB; Lee S; Regenhardt RW; McGarvey NH; Ayers JI; Notterpek L; Borchelt DR; Golde TE; Giasson BI. Intramuscular injection of α-synuclein induces CNS α-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci U S A. 2014. doi: 10.1073/pnas.1321785111.
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