Lipid Mediated Protein Functions

It is now well established that lipids not only form cellular membranes but also mediate a large variety of vital physiological functions by affecting the activity and/or localization of membrane associated proteins. In the majority of these cases, lipids and proteins co-localize in specialized membrane patches (domains), which exhibit physicochemical properties distinctively different from the properties of the surrounding biomembrane. The unique physicochemical properties of these specialized domains are crucial for the correct function of a multitude of proteins and failure in the proper assembly of these superstructures have been associated with a broad range of disease states, most notably cancer.

Inositol phospholipids (phosphoinositides) have been shown to be pivotal for a large variety of cellular processes. Physiologically relevant phosphoinositides are mono-, bis- or trisphosphorylated at the 3′,4′ or 5′ position of the inositol ring. Growing evidence suggests that the phosphate substitution pattern at the inositol ring has a marked influence on the physiological behavior of this important lipid class. Dr. Gericke’s research aims to understand the mechanisms that lead to the apparent compartmentalization of phosphoinositides and his research group investigates the physicochemical properties of phosphoinositide/protein complexes. In a related project area, the properties of sphingolipid containing model membrane systems are being characterized.

FTIR Imaging of Biological Systems

The functionality of complex systems can only be understood by analyzing both the molecular structure and the spatial distribution of the components. Infrared imaging microscopy is an extraordinarily versatile technique for the analysis of complex systems. Dr. Gericke’s research in this area is devoted to the development of new IR-laser based imaging techniques for the characterization of model membrane systems and biological tissue. These visualization efforts are complemented by fluorescence correlation spectroscopy and confocal microscopy measurements.

Students in Dr. Gericke’s research group will obtain practical training in standard analytical and biophysical techniques (e.g.; FTIR, NMR, DLS, Calorimetry Fluorescence Spectroscopy, and Fluorescence Correlation Spectroscopy). The scope of the research projects ranges from biophysically/biochemically oriented projects to instrument development. For more details, please feel free to visit the group webpage.

Selected Publications:

1. Redfern, R. E., Redfern, D., Furgason, M. L. M., Munson, M., Ross, A. H. & Gericke, A. PTEN Phosphatase Selectively Binds Phosphoinositides and Undergoes Structural Changes. Biochemistry 47, 2162-2171 (2008).

2. Kooijman, E. E., Sot, J., Montes, L. R., Alonso, A., Gericke, A., de Kruijff, B., Kumar, S. & Goni, F. M. Membrane organization and ionization behavior of the minor but crucial lipid ceramide-1-phosphate. Biophysical Journal 94, 4320-4330 (2008).

3. Mukherjee, R., Donnay, E. G., Radomski, M. A., Miller, C., Redfern, D. A., Gericke, A., Damron, D. S. & Brasch, N. E. Vanadium-vitamin B12 bioconjugates as potential therapeutics for treating diabetes. Chemical Communications (Cambridge, United Kingdom), 3783-3785 (2008).

4. Gericke, A. et al. Importance of phosphorylation for osteopontin regulation of biomineralization. Calcified Tissue International 77, 45-54 (2005).

5. Redfern, D. A. & Gericke, A. pH-Dependent domain formation in phosphatidylinositol polyphosphate/phosphatidylcholine mixed vesicles. Journal of Lipid Research 46, 504-515 (2005).

6. Brauner,J. W. , C.R. Flach, Z. Xu, X. Bi, R.N.A.H. Lewis, R.N.McElhaney, A. Gericke, R. Mendelsohn Quantitative functional group orientation in Langmuir films by Infrared Reflection Absorption Spectroscopy: C=O groups in behenic acid methyl ester and sn2 - 13C-DSPC; J. Phys. Chem. 107, 7202 – 7211 (2002).

7. Flach, C.R., Gericke, A., Keough, K.M.W. & Mendelsohn, R. Palmitoylation of lung surfactant protein SP-C alters surface thermodynamics, but not protein secondary structure or orientation in 1,2-dipalmitoylphosphatidylcholine Langmuir films. Biochim. Biophys. Acta1416, 11-20 (1999).

8. Gericke A., A. Kerth, A. Blume, “Infrared spectroscopic investigation of lipid and protein monolayers at the air/water interface,” Bruker Application Note 51 (1999)

 

Last Updated: 15 August 2008