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Regulation of forkhead box (FOX) transcription factors by protein kinase GSK3
Sweden (IFMSA-Sweden) - Linkopings Universitet, Linkoping
Clinical and Experimental Medicine (IKE), IKE/MMM – Plan 12, 581 83 Linköping, Sweden
Prof. Anders Fridberger
Stefan Koch, PhD, Senior Lecturer
Type of Research Project
- Basic science
What is the background of the project?
GSK3 is a ubiquitous, promiscuous serine/threonine kinase that controls cellular homeostasis in many tissues. We have found that forkhead box (FOX) transcription factors are GSK3 substrates, whose activity and stability is subject to phosphorylation- dependent regulation. Consequently, FOX transcriptional activity may be regulated by GSK3. Given that GSK3 activity itself is controlled by homeostatic as well as inflammatory signaling pathways, these observations suggest that a novel GSK3/FOX signaling axis governs tissue homeostasis. Our research thus has the potential to uncover therapeutic vulnerabilities related to FOX dysregulation, notably intestinal inflammation and cancers.
What is the aim of the project?
The aim of this project is to identify forkhead box (FOX) transcription factors under GSK3 control. Specifically, we intend to map the reciprocal regulation of GSK3 and FOX protein activity.
What techniques and methods are used?
We are using standard molecular biology assays to study protein stability and activity, in particular molecular cloning and immunoblotting. In the first step of this project, the student will clone relevant forkhead box (FOX) proteins from complementary DNA (cDNA) pools available in the lab into tagged expression vectors, and will then express these constructs in model cell lines. The student will then modulate GSK3 activity in these cells using pharmacological inhibitors and gain/loss-of- function plasmid vectors, and study FOX protein stability and activity under these conditions.
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?
The student is expected to actively participate in an ongoing research project relating to GSK3- dependent protein regulation, following good scientific practice. The student shall, under supervision, perform molecular biology assays (i.e. immunoblot, polymerase chain reaction (PCR), immunostaining), document results, and present these data to other group members in the weekly lab meetings. The student is further expected to summarize the work in our group in a scientific report at the end of his or her internship.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, weekly lab meeting and division lecture series.
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?
Biomedical education, good English language skills, basic molecular biology lab working experience. Prior experience with immunoblot or PCR are beneficial, but not required.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Koch S. Extrinsic control of Wnt signaling in the intestine. Differentiation. 2017 Aug 5;97:1- 8.
- Koch S; Acebron SP; Herbst J; Hatiboglu G; Niehrs C. Post-transcriptional Wnt signaling governs epididymal sperm maturation. Cell. 2015 Nov 19;163(5):1225-36.
- Koch S; Nusrat A. The life and death of epithelia during inflammation: lessons learned from the gut. Annu Rev Pathol. 2012;7:35-60.
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