Advanced Molecular and Cellular Medicine (E07I6A)
To provide an overview of the current field of molecular and cellular medicine, which is the development of new therapies based on progress in basic medical research.
To provide insights to the student in how new biomedical research findings can be applied in experimental therapy, illustrated with examples of a few important diseases.
To introduce the student in new biomedical research techniques.
Mode of examination
Oral exam with written preparation (outside normal exam period)
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2012 - 2013
- Think of a new strategy against HIV infection. - Which approach? - Which vector? - Target cells? - How to follow up?
Extra: can you use lentiviral vector for systemic treatment? Which vector can you use for this? Note: your answer will never be completely correct, since a student is not likely to find a way to eradicate HIV. Just give the best answer you can think of and already think of the flaws in your plan so the prof doesn't surprise you.
- we have found a protein which interact with HCV RNA polymerase;with yeast two hybrids method.we want to target this interaction with a new drug,how can we validate this new drug.
- Hematopoietic stem cells are manipulated (does not matter how). - How do you check if you still have hematopoietic stem cells? - Give at least two ways to expand the cells. - How can you improve engraftment?
Extra: Can you test for human HSCs through a competitive repopulation assay? If you go for a KO approach to improving engraftment, do you just KO random genes from the whole genome or do you start with specific genes? Note: She's very friendly and just wants you to think about things. Don't be afraid of giving a wrong answer, just make sure that you can argue why your way is a good way.
- we have a genetic disease in heart(laminopathy) which causes heart failure,we want to use stem cells for it.
a.which stem cells do you use.mention at least two ways. b.how can we correct the genetic defect c.how can we the test the ability of both genetically corrected and non corrected stem cells to differentiate into cardiomyocytes.
2013 - 2014
New mutation found in SHC2 gene, which leads to MSA. Symptoms are ataxia, parkinsonian-like, not dopaminergic-dependent. Postmortem Brain evaluation showed glial cytoplasmic inclusion bodies of alpha-synuclein.
Generate animal models to mimick the disease in 3 different species.
What are the (dis)advantages of each strategy
How would you validate those animal models?
a) what are pluripotent stem cells? How do you generate them? What are the ethical considerations?
b) hematopoietic SCs. How do you define that they are really HSCs? What animal studies do you use to prove this?
c) possible generation of Leukimic SCs. How do you determine this?
Trying to find a new biomarker for colon cancer, you have samples of healthy and diseased individuals
1) How to identify a new biomarker (>20kDa)
2) If you cannot find a difference in abundance, what would you investigate further?
3)How do you validate your biomarker?
4)What is the clinical significance of MRM?
2015 - 2016
New strategy against HIV
You want to develop an in vitro model for anencephaly: problems development neurons. Dominant disease, you know which gene is affected.
1. Mention at least 3 (stem) cell methods
2. There are problems in your in vitro model with proliferation and differentiation. How do you test this phenotype?
→ Answer: animal models (explain how to create them)
3. You want to do transcriptome analysis. How?
→ Answer: sequencing
4. You’re transcriptome analysis revealed problems with Wnt. What can it be? And how do you test it?
→ explain if over/underexpression (this was clear with notes from lecture stem cell and information given in question) → How test? Wnt was overexpressed → add Wnt to in vitro models of healthy cells and see if problems develop…..
2017 - 2018
1. A new equine retrovirus (EIAV) has been picked up recently. You are heading a research group that aims to develop a novel functional and safe viral vector platform for gene therapeutic approaches.
a) Explain how you would engineer this vector system and discuss necessary adaptations in you design to ensure safe use
b) How would you use this platform to generate a cell-based model to study a genetic immune disorder, that is caused by an autosomal gain of function mutation in the Stat3 gene. Structure of the retrovirus genome provided (max 1 page)
2. How do you validate that a protein is a genuine target to treat a human disease.
3. Debyser: How would you do target validation to prove a target can be therapeutically effective
4. Derua: You are working in a well-equipped proteomics lab. Project: find a protein biomarker for colon cancer using biopsies of healthy and diseased people. Explain detailed 1 strategy to find the protein biomarker. How would you validate the candidate biomarker? What are pitfalls and advantages of MS driven clinical proteomics?
5. Baekelandt: A recessive autosomal mutation is given, with parkinson-like symptoms. Which animal model would you use?
6. Debyser: How to validate a good target for a human disease?