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A cell based model development for Alzheimer’s Disease
Turkey (TurkMSIC) - Yeditepe University, Istanbul
Immunology Department, Medical School, Yeditepe University Inonu Mah., Kayisdagi Cd. No:326A, 34755 Atasehir/Istanbul
Prof. Dr. Gulderen Yanikkaya Demirel
PhD student Basak Aru
Type of Research Project
- Basic science
What is the background of the project?
Alzheimer is regression of brain functions. Alzheimer's disease (AD) has been identified as a protein misfolding disease (proteopathy), caused by plaque accumulation of abnormally folded amyloid beta protein (Aβ) and tau protein in the brain. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus coeruleus, amygdala, substantia nigra, striatum, and claustrum. Several recent studies have examined the relationship between Aβ and N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid β-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. There are currently 47 million Alzheimer's patients in the world and 600,000 families in Turkey are struggling with this disease. About the project; gene transfer phase is already done. Students who are able to come during Jan. 2020 – June 2020 can attend to gene silencing/activation studies. Project goes on until 2021 but students will be accepted to the period above. The Immunology department in our university has been established in 2011 by the project supervisor Prof. Dr. Gulderen Yanikkaya Demirel.
What is the aim of the project?
The aim of this project is to develop an in vitro cell based model of Alzheimer Disease to explore the mechanisms of the disease.
What techniques and methods are used?
Gene transfer to microorganisms (Vector design) Cell culture) Gene transfer is an increasingly utilized approach for research and clinical applications involving the central nervous system (CNS). Vectors for gene transfer can be as simple as an unmodified plasmid, but more commonly involve complex modifications to viruses to make them suitable gene delivery vehicles.The current capabilities of plasmid, retroviral, adeno-associated virus, adenovirus, and herpes simplex virus vectors for CNS gene delivery will be described. These include both focal and global CNS gene transfer strategies, with short- or long-term gene expression. Infection of neural progenitors with these microorganisms Neural progenitor cells are responsible for populating the developing central nervous system with neurons and glia. Neural progenitor dysfunction can lead to severe birth defects, namely, lissencephaly, microcephaly, and cognitive deficits(Cell culture, vector use, characterization of related protein profile (Western Blot) Western Blot consists of 3 main phases: I)Separation of Proteins, II) Transfer of Proteins, III)Probing and Detecting Proteins. Gene silencing/activation studies using RNAi(Ribonucleic Acid Interference) and ASOs(antisense oligonucleotides) Gene level DNA replication (Polymerase chain reactions)
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
What are the tasks expected to be accomplished by the student?
The student will observe or perform under supervision the following tasks: -Recognizes the known genes and factors that causes Alzheimer disease. -Examining the lateral gene transfer (LGT) and horizontal gene transfer (HGT) methods that will be done by the tutor. -Observing the tests that will be done in the laboratory -Preparing a presentation at the end of the research term about the research project. -Implementing their research with the possible reagents and measurement devices in the lab - Learning the viral vector, non-viral vector types advantages and disadvantages - Observing the viral vector design system
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
The following topics will be provided in the form of seminars by Prof.Dr.Gulderen Yanikkaya Demirel. Lessons will be provided according to the availability of the teacher, at least once per week: -Gene transform of microorganisms able to design vector and cell culturing -Vaccination importance for infectious diseases. -Viral vector design and production systems for three of the most widely used viral vectors: Adenovirus, Adeno-Associated Virus, and Lentivirus. - Western Blot consists of 3 main phases: I)Separation of Proteins, II) Transfer of Proteins, III)Probing and Detecting Proteins.
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
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No specific skills are required.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system
- Kocahan S. And Dogan Z.; Mechanisms of Alzheimer’s Disease Pathogenesis and Prevention: The Brain; Neural Pathology; N-methyl-D-aspartate Receptors; Tau Protein and Other Risk Factors. Clin Psychopharmacol Neurosci. 2017 Feb; 15(1): 1–8. DOI: 10.9758/cpn.2017.15.1.1
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