Ruprecht-Karls-Universität Heidelberg
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Fuellekrug0117 - Scientist (f/m) / PhD position
Project no:
Fuellekrug0117

Project leader:

Project supervisor:
Füllekrug, Joachim
Application deadline:
31. Jul 2018
Start of PhD project:
1. Aug 2018

Project description:

Title:
Transendothelial fatty acid transport
Summary:
The overall key question of this project is: Which is the molecular mechanism for the favored transport of fatty acids across the endothelium as opposed to their metabolism by the endothelial cells? Driving forces for the transport of fatty acids are in principle: regulation by fatty acid transport proteins, concentration differences between luminal and abluminal endothelial plasma membrane, higher velocity of transport as compared to metabolism, and the protection of non-esterified fatty acids against the cytosolically oriented CoA ligases. These hypotheses will be examined by the work program, and correlated to each other. The expression level of the candidate proteins is going to be modified by retrovirus mediated RNA interference or overexpression respectively. Immortalized (HMEC-1) as well as primary cultures of peripheral microvascular endothelial cells (HUVEC) will be differentiated on permeable filters to be able to measure fatty acid transport and metabolism simultaneously. The focused project aims derived from the hypotheses are:
1. Elucidation of the mechanism of action of the FATP transporters.
2. Identification of the underlying dominant determinants for the high velocity of fatty acid transport as compared to endothelial metabolism.
3. Investigation if cytosolic proteins or caveolae protect non-esterified fatty acids from the metabolic enzymes.
References:
Küch, E., Vellaramkalayil, R., Zhang, I., Lehnen, D., Brügger, B., Stremmel, W., Ehehalt, R., Poppelreuther, M. and J. Füllekrug (2014). Differentially localized acyl-CoA synthetase 4 isoenzymes mediate the metabolic channeling of fatty acids towards phosphatidylinositol. BBA Mol Biol Cell Lipids 1841, 227-239.

Digel, M., Staffer, S., Ehehalt, R., Stremmel, W. and J. Füllekrug (2011). FATP4 contributes as an enzyme to the basal and insulin mediated fatty acid uptake of C2C12 muscle cells. Am J Physiol Endocr Metab. 301, 758-96.

Milger, K., Herrmann, T., Becker, C., Gotthardt, D., Zickwolf, J., Ehehalt, R., Watkins, P.A., Stremmel, W. and J. Füllekrug (2006). Cellular uptake of fatty acids driven by the ER localized acyl-CoA synthetase FATP4. J Cell Sci. 119, 4678-88.
Methods that will be used:
primary cell culture (HUVECs)
retroviral shRNA/cDNA expression
radiolabeled fatty acids
transwell transport assays
immunolocalization
Cooperation partners:
tbd during the project
Personal qualifications:
MSc of Biochemistry, Molecular Biology, or related
Preferably experience with tissue culture and/or biochemical assays
Keywords: