Mark Bowen
	Asst. Professor Department of Physiology and Biophysics Basic Science Tower 5-124 State University of New York Stony Brook, NY, 11794-8661   Phone 631-444-2536 Fax 631-444-3432   Email: mark.bowen at sunysb.edu
	Ph. D, Biochemistry, 1998 University of Illinois, Chicago Medical Center   B.A. , Chemistry, 1991 University of Minnesota, Morris

My lab is interested in understanding the molecular underpinnings of synaptic transmission.  The regulated communication between neurons underlies all that makes us human: learning, memory and emotion.  When communication goes awry the result is mental illness, neurodegenerative disease and death.  By understanding the molecular basis of synaptic function, pharmaceutical strategies for intervening become possible.

When a neuron receives a signal, in the form of neurotransmitters, it must make a binary decision: to propagate the signal of remain at rest.  The probability of response is tuned by the history of activity at the synapse.  This tuning occurs in the post synaptic density, a signal processing machine containing hundreds proteins including cytoskeletal elements, receptors, ion channels and their associated signaling proteins, held together by scaffold proteins.

My lab focuses on the MAGUK (Membrane Associated GUanlyate Kinase) family of scaffolds.  Composed of a catalytically inactive guanylate kinase domain, an SH3 domain and three PDZ domains, MAGUK proteins localize and organize glutamate receptor signaling.  Great progress has been made in identifying proteins at the synapse and in studying their binary interactions.  The structure and binding affinities of the individual MAGUK domains is known.  My lab seeks to extend this knowledge by studying the structure and dynamics of multiprotein complexes reconstituted from purified components.  To sort out the heterogeneity in these complex mixtures, we use single molecule fluorescence microscopy to follow individual complexes.  

We aim to understand how MAGUK proteins regulate the availability of binding sites through structural rearrangement, and determine how MAGUK binding partners interact with each other in higher order complexes.  Scaffold proteins are hubs in the network of protein interactions.  By learning the relative weights of interactions at the scaffold, we will come closer to predicting the output of this network. 

Selected Publications

Bowen M & Brunger AT.   "Conformation of the synaptobrevin transmembrane domain."  Proc Natl Acad Sci USA. 2006 May 30;103(22):8378-83    Medline

 Dennison SM, Bowen ME, Brunger AT & Lentz BR.  “Neuronal SNAREs do not trigger fusion between synthetic membranes but do promote PEG-mediated membrane fusion.”  Biophys J. 2006 Mar 1;90(5):1661-75    Medline

 Bowen ME, Weninger K, Ernst J, Chu S &Brunger AT.  “Single-molecule studies of synaptotagmin and complexin binding to the SNARE complex.”   Biophys J. 2005 Jul;89(1):690-702    Medline

 Bowen ME, Weninger K, Brunger AT & Chu S.  “Single molecule observation of liposome-bilayer fusion thermally induced by soluble N-ethyl maleimide sensitive-factor attachment protein receptors (SNAREs).”  Biophys J. 2004 Nov;87(5):3569-84   Medline

 Weninger K, Bowen ME, Chu S & Brunger AT.  “Single-molecule studies of SNARE complex assembly reveal parallel and antiparallel configurations.”  Proc Natl Acad Sci USA. 2003 Dec 9;100(25):14800-5    Medline

 Bowen ME, Engelman DM,  & Brunger AT.  “Mutational analysis of synaptobrevin transmembrane domain oligomerization.”  Biochemistry. 2002 Dec 31;41(52):15861-6.   Medline