Many signalling pathways in the cell are regulated by molecular switches that can be activated and inactivated under a variety of circumstances. We study in particular small GTPases. They cycle between an active GTP-bound state and an inactive GDP-bound state. In its active state the GTPases interact with a multitude of effectors that relay upstream signals to celluar components to elicit an effect, for example re-organisation of the cytoskeleton. We are currently investigating a small GTPase called RhoBTB3. RhoBTB proteins participate in regulation of vesicle transport and of the cell cycle, and they have been also described as tumour suppressors but little is known about their mechanism of action. To clarify this we are characterizing animals that do not produce RhoBTB3 and as a consequence show alterations in their skeleton.
Interested students will have the opportunity to quantify these alterations in PET (positron emission tomography) scans of mice lacking RhoBTB3 and their wild type counterparts. The work will involve measuring bone sizes from three-dimensional renderings of the PET scans at the computer, followed by statistical analysis.
1. A few paragraphs on small GTPases of the Ras superfamily, then narrowing down to the Rho family (to which RhoBTB3 belongs).
2. More detail about RhoBTB in general, then RhoBTB3 in particular, including where it is expressed. Here you go into details about proposed RhoBTB3 functions and mention our work on the Rhobtb3 knockout (I forwarded you the paper some time ago). You are welcome to include a picture from that paper showing expression of RhoBTB3 in cartilage and bone, that would provide the link towards your working hypothesis.
3. Some information about the mouse skeleton and development of the skeleton in that animal.
4. Some background about the CT scan.
The next section is your hypothesis and how you want to address it. In a few words, it’s like follows:
Rhobtb3 is highly expressed in cartilage and bone
Rhobtb3 KO mice have a growth defect and (mentioned in our paper) defective patellae
So we wanted to do a thorough quantitative investigation of the whole cytoskeleton using a method that allows visualisation and measurements
Then you have your methods section where you describe how you collected and analysed data. provide Cartoons of the mouse skeleton to illustrate what you did.
Then your results. Show images, that always impresses.
Now, coming to literature, there is not an awful lot on RhoBTB3, so you can make a literature search of the last few years. Older stuff is reviewed in Berthold et al, Acta Pharmacol Sin (cited in our paper). In our paper, in the introduction, you will find some relatively recent work mentioned there. I suggest you take that introduction as a guidance and you bring your intro a bit beyond that, adding further details where you feel you would add them. i need like 500 more words in the introduction and 2500 words on the discussio
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