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Identifications of the molecular mechanisms responsible for the selective motor neuron death causing amyotrophic lateral sclerosis (ALS)
Belgium (BeMSA) - KU Leuven, Leuven
Laboratory of Neurobiology
Dr. L. Van Den Bosch
Type of Research Project
- Basic science
What is the background of the project?
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective death of motor neurons in the motor cortex, brainstem and spinal cord. This results in muscle weakness, paralysis and death of the patient on average 3 to 5 years after the diagnosis. In the Laboratory of Neurobiology, we use a broad variety of models and techniques to investigate the pathogenic mechanisms responsible for this dramatic neurodegenerative disease. In addition, we search for modifiers that can influence the disease process. The models used include (primary) cell cultures, induced pluripotent stem cells, fruit flies, zebrafish, mice and rats. A wide variety of techniques are available to monitor the disease process in these models. Ultimately, we hope to contribute to a better understanding of the molecular mechanisms responsible for the selective motor neuron death which could lead to the development of new therapeutic strategies.
What is the aim of the project?
To investigate the pathological mechanisms responsible for the selective motor neuron death using zebrafish as a model.
What techniques and methods are used?
Zebrafish will be used for this specific project. First we will inject mRNA in fertilized zebrafish eggs and evaluate the effect on the development of the zebrafish embryos and the development of the motor axons. The injected RNA encodes proteins that can influence the disease process. Thirty hours post fertilization, the embryos are fixed and the motor axons are stained using an antibody directed against the SV2 (Synaptic vesicle 2) protein. Both the length and the branching of the motor axons is quantified using an in house developed software program.
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Firstly the student will micro inject vectors with mRNA into fertilized zebrafish eggs. Afterwards (s)he will extract the RNA and amplify it with PCR (polymerase chain reaction). After these steps different techniques will be used. The student will perform western blot for the fixation and staining of zebrafish embryos. Afterwards the student will evaluate the motor neuron growth by Immunohistochemically staining. After all the data are collected, the statistical analysis will be performed with SPSS (Statistical Package for the Social Sciences). All tasks will be performed under supervision of a PhD student.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes. Student should do some preliminary reading on the topic. Tutors will answer theoretical questions.
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 presentation
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic knowledge of cell biology and physiology
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Students in biomedical fields
- Van Hoecke A et al. (2012) EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nature Medicine 2012; 18 (9); 1418-1422
- Swinnen B. et al. (2018) A zebrafish model for C9orf72 ALS reveals RNA toxicity as a pathogenic mechanism. Acta Neuropathol. 2018 Jan 4. doi: 10.1007/s00401-017- 1796- 5.
- Van Damme P. et al. Modelling amyotrophic lateral sclerosis: progress and possibilities. Dis Model Mech. 2017 May 1;10(5):537-549. doi: 10.1242/dmm.029058.
- Bento-Abreu A. et al. (2018). Elongator subunit 3 (ELP3) modifies ALS through tRNA modification. Human Molecular Genetics; Ahead of print; art.nr. 10.1093/hmg/ddy043.
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