Projects
Name
Targeting cholesterol metabolism of cancer cells as a new therapeutic pathway
University
Turkey (TurkMSIC) - Istanbul Medeniyet University LC, Istanbul
Domain
Biology
Departement
Istanbul Medeniyet University Medical Faculty Department of Medical Biology, Unalan street, D-100 Highway, 34700 Uskudar/Istanbul
Head
Dr. Burcu YUCEL
Tutor
Dr. Burcu YUCEL
Languages
Turkish, English
Duration
4 weeks
Availability
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No Yes No No No No No
Type of Research Project
- Basic science
What is the background of the project?
Please, provide the background of the project (Provide information about the project; min. 10 lines, max. 25 lines) Cholesterol is a non-essential metabolite for normal cell growth and proliferation as most normal cells are capable of making it de novo from Acetyl-CoA. Even though components and regulation of cholesterol metabolism is mechanistically well described in normal physiology, cholesterol metabolism of cancer cells with diverse origins and genotypes has not been previously explored. In my preliminary work, I discovered that, unlike most normal cells, a small group of cancer cells are remarkably dependent on extracellular cholesterol. This suggests that the same group of cancer cells likely carry defects in de novo cholesterol biosynthesis and is therefore auxotrophic for cholesterol.
What is the aim of the project?
Main aim is to identify the mechanistic basis of cholesterol auxotrophy in cancer cells and determine if this metabolic liability could be exploited for therapy.
What techniques and methods are used?
What techniques and methods are used? Mention the steps/stages in this project. (Provide examples and avoid abbreviations; which tools will be used in general in this project?) -The usage of cell cultures for the proliferation of the cells Cell culture is one of the major tools used in cellular and molecular biology, providing excellent model systems for studying the normal physiology and biochemistry of cells (e.g., metabolic studies, aging), the effects of drugs and toxic compounds on the cells, and mutagenesis and carcinogenesis. -Gene cloning with Polymerase Chain Reaction (PCR): PCR is a common tool used in medical and biological research labs. It is used in the early stages of processing DNA for sequencing, for detecting the presence or absence of a gene to help identify pathogens during infection, and when generating forensic DNA profiles from tiny samples of DNA. -CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) genome editing: The CRISPR/Cas9 system has been harnessed to create a simple, RNA-programmable method to mediate genome editing in mammalian cells, and can be used to generate gene knockouts (via insertion/deletion) or knockins (via HDR). To create gene disruptions, a single guide RNA (sgRNA) is generated to direct the Cas9 nuclease to a specific genomic location. Cas9-induced double strand breaks are repaired via the NHEJ DNA repair pathway. The repair is error-prone, and thus insertions and deletions (INDELs) may be introduced that can disrupt gene function. -Western Blotting: Western blot is often used in research to separate and identify proteins. In this technique a mixture of proteins is separated based on molecular weight, and thus by type, through gel electrophoresis. These results are then transferred to a membrane producing a band for each protein. The membrane is then incubated with labels antibodies specific to the protein of interest.
What is the role of the student?
- The student will mainly observe
- 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?
What techniques and methods are used? Mention the steps/stages in this project. (Provide examples and avoid abbreviations; which tools will be used in general in this project?) -The usage of cell cultures for the proliferation of the cells Cell culture is one of the major tools used in cellular and molecular biology, providing excellent model systems for studying the normal physiology and biochemistry of cells (e.g., metabolic studies, aging), the effects of drugs and toxic compounds on the cells, and mutagenesis and carcinogenesis. -Gene cloning with Polymerase Chain Reaction (PCR): PCR is a common tool used in medical and biological research labs. It is used in the early stages of processing DNA for sequencing, for detecting the presence or absence of a gene to help identify pathogens during infection, and when generating forensic DNA profiles from tiny samples of DNA. -CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) genome editing: The CRISPR/Cas9 system has been harnessed to create a simple, RNA-programmable method to mediate genome editing in mammalian cells, and can be used to generate gene knockouts (via insertion/deletion) or knockins (via HDR). To create gene disruptions, a single guide RNA (sgRNA) is generated to direct the Cas9 nuclease to a specific genomic location. Cas9-induced double strand breaks are repaired via the NHEJ DNA repair pathway. The repair is error-prone, and thus insertions and deletions (INDELs) may be introduced that can disrupt gene function. -Western Blotting: Western blot is often used in research to separate and identify proteins. In this technique a mixture of proteins is separated based on molecular weight, and thus by type, through gel electrophoresis. These results are then transferred to a membrane producing a band for each protein. The membrane is then incubated with labels antibodies specific to the protein of interest.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Lessons about the cholesterol metabolism and cancer metabolism will be provided in the form of seminars by Dr. Burcu YUCEL. Lessons will be provided each once according to the availability of the teacher
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
No
Hours
8
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- Pre-Medical students from the American-British system
- Students in biomedical fields
- Dental medicine students (IADS members)
Articles
- Garcia-Bermudez J. et al. Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death. Nature 2019 Mar;567(7746):118-122. doi:10.1038/s41586-019-0945-5