Personnel
Anja Nohe
Department of Chemical and Biological Engineering
University of Maine, Orono
207 Jenness Hall
(207) 581-2270
anohe@umche.maine.edu
http://www.umche.maine.edu/chb/
faculty/anohe.htm
Lab Members:
Kira Young, Graduate Student
Beth Bragdon, Research Assistant
James Cook, Undergraduate
Joshua Verril, Undergraduate
Research:
The Family of Image Correlation Spectroscopy (FICS)
FICS is a powerful tool to analyze the distribution aggregation and clustering of membrane proteins on the cell surface. Our lab is interested in the further development of these techniques by analyzing the autocorrelation and cross-correlation functions in more detail.
Dynamics of Membrane Domains. Membrane proteins are not distributed uniformly on the cell membrane. Many of them are aggregated in clusters and localized in special membrane domains. There are at least three important domains known on the cell surface, rafts, caveolae and coated pits. These domains are thought to be either signaling centers (rafts, caveolae) or responsible for the endocytosis of proteins (coated pits). Although there is much known about proteins localizing with these domains using molecular biology techniques there is not much known about the dynamics of the domains themselves on the cell surface.
Dynamic Image Correlation Spectroscopy, a technique used to analyze the dynamics of proteins on the cell surface, was used to examine the diffusion of key proteins associated with rafts (GPI anchored proteins), caveolae (caveolin-1) and coated pits (AP-2) on live cells at various temperatures. We further examined the state of aggregation and the cluster density of these proteins. We are developing a model to understand the dynamics of membrane proteins and their diffusion. (Anja Nohe (UMaine, Orono, USA), (James Cook, Undergraduate Student, UMaine) Gisou van der Goot (University of Geneva, Geneva, Switzerland), Pascal Valloton, Diatrack, Lausanne, Switzerland)
Signal Transduction of Bone Morphogenetic Proteins. Bone Morphogenetic Proteins (BMPs) play a crucial role during all stages of embryonic development. Over 30 different BMPs mediating different responses are known; whereas only 6 receptors have been identified. This raises the question of the specificity of BMP signaling. For initiation of signaling, at least one type-I and one type-II receptor are necessary. Presently only two major downstream signaling pathways have been identified, which can be activated by any receptor combination. Little is known about the signal specificity and even less about the BMP-receptor internalization. Our data indicate that lipid domains play an important role in the regulation of the signaling on the cell surface.
We identified 3 proteins and are currently investigating the function of these proteins in the signal transduction of BMPs. We are further interested in the interaction of Endoglin on BMP signaling. (Cal Vary (MMRCI, Scarborough, USA), Kira Young (Graduate Student, UMaine, Orono, USA), Beth Bragdon (Research Assistant, UMaine, Orono, USA), and Anja Nohe (UMaine, Orono, USA). Three other projects involve Nick Morell (Cambridge U.K), Eileen Shaw (University of Pennsylvenia, USA) and Fabian Pohl (University of Wuerzburg, Germany) to use ICS to determine the aggregation and clustering of BMP receptors in diseases like PPH (Primary pulmonary Hypertension), FOP and HO (Heterotopic Ossification).
Signal Transduction of EGF Receptors. EGF signaling plays a crucial role in cell proliferation and survival. One of the most studied receptors is the EGFR, a tyrosine kinase receptor. To understand the early steps involved in the activation of the signalling we are interested to understand the aggregation and clustering of EGFR on the cell surface, especially how EGF stimulation can change the aggregation and the distribution of clusters. Kira Young is measuring the dynamics of EGF and EGF receptors using EGF coated QDs (Jay Nadeau, McGill University, Montreal, Canada).
The crosstalk of BMP receptors and EGF receptors on the membrane level is also under investigation (Anja Nohe, Nils Petersen, Nora Keating).
Recent publications
Nohe A, Petersen NO. 2004. Analyzing for co-localization of proteins at a cell membrane. The single way down from single genes, and proteins to single molecules. Curr Pharm Biotech 5:213-220.
Nohe A, Petersen NO. 2004. Analyzing the protein-protein interactions in cell membranes. Bioessays 26:196-203.
Kovar M, Nohe A, Petersen NO, Norton P. 2004. Optical imaging using NSOM. Photonics Handbook. Laurin publishing. H77-80
Nohe A, Keating E, Loh C, Underhill MT, Petersen NO. 2004. Caveolin-1 isoform reorganization studied by Image Correlation Spectroscopy. Faraday discussion. 126:185-195
Nohe A, Keating E, Knaus P, Petersen NO. 2004. Signal transduction of bone morphogenetic protein receptors. Cell Signal 16:291-299.
Pohl F, Koelbl O, Flentje M, Nohe A. 2005. Analysis of the formation of heterotopic ossifications in a cell model - Effects of irradiation on cellular signalling regarding the BMP-receptors in Cellular Signaling: New Research. Nova publishing.
Nohe A, Keating E, Underhill TM, Knaus P, Petersen NO. 2005. Dynamics and interaction of caveolin-1 isoforms with BMP-Receptors. JCS (in press).
Nohe A, Keating E, van der Goot G. Petersen NO. Dynamics of GPI-anchored proteins on the surface of living cells. Nanomedicine (in press).
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