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Generation of α-synuclein reporter iPSC lines using CRISPR/Cas9 for studies on Lysosomal Storage Disorders

Reyhani, Samira (2022) MOBN02 20221
Degree Projects in Molecular Biology
Popular Abstract
Generation of cell model using stem cells and genome engineering to study lysosomal storage disorders

Lysosomal storage disorders (LSDs) are a group of approximately 70 diseases and many cause childhood neurodegeneration. There is no treatment for neurological symptoms of LSDs due the complexity of nervous system and lack of accurate study models. Stem cells are a promising tool to be used for studying different diseases as they can differentiate into different cell types and recapitulate the molecular mechanisms of a disease.

A strong genome engineering tool, called CRISPR/Cas famous as ‘the DNA scissors’, can be used to add fluorescent or non-fluorescent tags to proteins inside the cell, enabling us to investigate protein... (More)
Generation of cell model using stem cells and genome engineering to study lysosomal storage disorders

Lysosomal storage disorders (LSDs) are a group of approximately 70 diseases and many cause childhood neurodegeneration. There is no treatment for neurological symptoms of LSDs due the complexity of nervous system and lack of accurate study models. Stem cells are a promising tool to be used for studying different diseases as they can differentiate into different cell types and recapitulate the molecular mechanisms of a disease.

A strong genome engineering tool, called CRISPR/Cas famous as ‘the DNA scissors’, can be used to add fluorescent or non-fluorescent tags to proteins inside the cell, enabling us to investigate protein expression, function, localisation, and its transmission between cells. These tags make it easier for us to distinguish the protein of our interest from thousands of other proteins inside or outside the cells. One of the proteins that is not fully studied yet is alpha-synuclein. It is found mainly in the nervous system and has shown to have important roles in neurotransmission. Aggregates of alpha-synuclein can lead to diseases such as Parkinson’s disease, Lewy Body disease, and are found in some LSDs. In LSDs, defects in an intracellular organelle called lysosome, which is responsible for degrading macromolecules, leads to accumulation of alpha-synuclein inside the cell. These accumulations are toxic to cells and can cause cell death and trigger neurological symptoms.

It is challenging to study and treat neurological symptoms because the brain is covered with a thin protective layer called blood-brain barrier which blocks the crossing of macromolecules, making it difficult to transfer therapeutic agents to brain cells. Research in this field is still going on and having better study models will help to identify new therapeutic option. Regarding animal models, their nervous system is very different to the human, and they do not accurately represent the human diseases. In addition, ethical issues of using animals for research is of consideration. Therefore, stem cell models can be a promising tool for studying the human nervous system and its disorders.

Stem cells can be differentiated into various cell types including brain cells. Nowadays, stem cells can be produced from reprogramming of skin cells, and they are called induce pluripotent stem cells (iPSCs). In this study we tagged alpha-synuclein in iPSCs using CRISPR/Cas9 and we generated 3 cell lines that will be used for future studies on LSDs. (Less)
Please use this url to cite or link to this publication:
author
Reyhani, Samira
supervisor
organization
course
MOBN02 20221
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9103302
date added to LUP
2022-11-17 11:53:33
date last changed
2022-11-17 11:53:33
@misc{9103302,
  author       = {{Reyhani, Samira}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Generation of α-synuclein reporter iPSC lines using CRISPR/Cas9 for studies on Lysosomal Storage Disorders}},
  year         = {{2022}},
}