Projects
Name
Ubiquitin-dependent processes in pathogenesis of Alzheimer's disease
University
Russian Federation (HCCM-Russia) Nizhny Novgorod State Medical Academy, Nizhny Novgorod
Domain
Pathophysiology
Departement
Central Research Laboratory
Head
Prof. Irina V. Mukhina
Tutor
Tatiana F. Sergeeva
Languages
English, Russian
Duration
4 weeks
Availability
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No Yes Yes No No No No No No No No No
Type of Research Project
- Basic science
What is the background of the project?
In the project the influence of inhibitors of ubiquitin-dependent processes on cofilin ubiquitylation and functioning of mitochondria will be studied. There will be performed a comparative analysis of the cell response in primary cultures of dissociated hippocampal cells obtained from healthy mouse embryos and 5X FAD (five familial Alzheimer's disease mutations ) mutant mouse embryos (Alzheimer's disease model). This project will allow to approach the understanding of molecular mechanisms of Alzheimer's disease pathogenesis, the ways of their regulation through ubiquitin-dependent processes.
What is the aim of the project?
The project aims to study the molecular mechanisms of Alzheimer's disease pathogenesis (mitochondrial dysfunction, the level and activity of the actin-binding protein cofilin) and the possibility of their correction at the level of ubiquitin-dependent processes.
What techniques and methods are used?
The assesment of cofilin expression, cofilin ubiquitylation will be performed by the methods of western blotting and immunocytochemistry in primary cultures of dissociated hippocampal cells derived from healthy mouse embryos. The intensity of tissue respiration in neurons will be estimated using the method of high-resolution respirometry
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Western blotting of cofilin and ubiquitin will be performed by the student on his/her own. Analysis of western blotting data and cofilin ubiquitylation will be performed by the student under supervision. Study of the effect of ubiquitin-proteasome system inhibitors on cofilin level and/or activity will be performed by the student under supervision.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Seminars: 1. The ubiquitin-proteasome system (Tatiana F. Sergeeva). 2. Western blotting (Natalia S. Maksimova).
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 scientific report
- The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Subjects passed: Biochemistry, Physiology, Molecular Biology Previous experience with: Working with Laboratory Equipment
Are there any legal limitations in the student’s involvement
No
Hours
7
Type of students accepted
This project accepts:
- Medical students
- Pre-Medical students from the American-British system
- Students in biomedical fields
Articles
- Bamburg JR; Bernstein BW.Actin dynamics and cofilin-actin rods in alzheimer disease.Cytoskeleton (Hoboken). 2016 Sep;73(9):477-97. doi: 10.1002/cm.21282._
- Gainullin MR; Zhukov IY; Zhou X; Mo Y; Astakhova L; Ernberg I; Matskova L.Degradation of cofilin is regulated by Cbl; AIP4 and Syk resulting in increased migration of LMP2A positive nasopharyngeal carcinoma cells.Sci Rep. 2017 Aug 21;7(1):9012. doi: 10.1038/s41598-017-09540-3._