Developing Advanced Fluorescence Technologies for Investigating Protein-Ligand Interactions
Project: Cells contain a multitude of receptor proteins that recognize specific ligands in the environment and use this information to guide decision making. The binding of ligands to receptor proteins eventually leads to cell signaling but the actual pathway taken is typically unknown. Ligand binding can lead to dimerization or oligomerization, to dissociation of preformed complexes or to conformational rearrangement of the receptor protein. Elucidation of ligand-receptor interactions is very important for understanding cell biology as well as the development of medication.
In my group, we develop advanced fluorescence technologies and apply them to interesting biological problems. These include single molecule microscopy, super resolution microscopy and fluorescence fluctuation spectroscopy. The goal of this PhD project is to develop and apply fluorescence methods to investigate receptor-ligand interactions. Initially, interactions of the G- protein coupled receptors (GPCR) with different ligands will be investigated using fluorescence fluctuation spectroscopy. Image cross correlation spectroscopy will be used in living cells to measure the affinity of the receptors for different ligands. The PhD student will also develop other fluorescence approaches such as metal enhanced fluorescence or super resolution microscopy with the aim of visualizing observe the changes in stoichiometry and in conformation induced by ligand binding in single complexes within live cells even at concentrations where normal single-molecule approaches are not possible.
We offer the PhD student an interdisciplinary work environment with graduate students and postdoctoral researchers expertise in physics, chemistry, biochemistry and biology. My laboratory is well equipped with 11 different advanced fluorescence microscopes.
Requirements: Candidates must be highly motivated, hard working and interested in interdisciplinary research, optical microscopy, quantitative analysis and biology. A degree in physics, physical chemistry, engineering, biochemistry or a related subject is recommended. Experience in optics, fluorescence microscopy and/or cell biology is beneficial but not necessary.
Recent related publications from my group include:
Hendrix J*, Schrimpf W, Höller M, Lamb DC*. Pulsed interleaved excitation fluctuation imaging. Biophys J 2013 105:848-861.
Ozgen H, Schrimpf W, Hendrix J, de Jonge JC, Lamb DC, Hoekstra D, Kahya N, and Baron W. The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix. PloS one 2014 9: e101834.
Group: Prof. Don Lamb, Department of Chemistry, LMU Munich
Prof. Lamb's website