Structure and function of transporters in neurons


 

The aim of my research is to elucidate the molecular function, architecture, and high-affinity drug binding sites of synaptic vesicle transporters in neurons by studying their function using biochemical techniques and determining their structures using single particle cryo-EM. I am particularly interested in understanding the conformational changes and mechanism associated with transporters. I have developed methods for large-scale expression, stabilization by drugs, and for the production of antibodies which recognize transporters. The use of transporter-antibody complexes is essential in order to provide mass and molecular features to assist in cryo-EM reconstructions because these transporters are small membrane proteins which are largely ensconced within membrane. Atomic structures of transporters in complex with therapeutic drugs are essential for the design of better small-molecule therapeutics with higher specificity and fewer side-effects and will also advance efforts toward understanding the function of these transporters.

 

 


Education

Aarhus University, Department of Physiology
Visiting student in lab of Dr. Jens Peter Anderson, 2010 

University of British Columbia, Department of Biochemistry and Molecular Biology
Ph.D. in lab of Dr. Rober Molday, 2007-2013

Postdoctoral Training

Oregon Health & Science University, Vollum Institute
Postdoctoral training in lab of Dr. Eric Gouaux, 2013-2020




Mail to:
Jonathan Coleman
2054 BST3
3501 Fifth Avenue
Pittsburgh, PA 15213

Phone: (412) 648-8077
Fax: (412) 648-9008

E-mail: coleman1@pitt.edu

Website link: coming soon

 


 

 

Photo of Faculty MemberOur lab is interested in developing new tools for mapping 3D organization of biomolecules and probing biological processes in the tissue and organism.

Complex biological systems are delicate machines consist of building blocks (such as proteins, nucleic acids, lipids, and carbohydrates) that are precisely organized in the nanoscale. This presents a fundamental challenge for humanity to understand the biology and/or pathology underlying these complex systems. To gain the insight into physiological/pathological functions, one might need to map a large diversity of nanoscale building blocks, over a wide spatial scale. To tackle this challenge, we are developing a set of novel technologies that enable large scale visualization of biological samples with nanoscale precision, by physically expanding the sample rather than magnifying the light from the sample via lenses. This principle is called expansion microscopy (ExM). By combining various material engineering and chemical approaches, we are advancing ExM-based tools that may elucidate biological insights into the brain and other complex systems, such as cancer and infectious diseases.


 

Education

B.S. Chemistry, 2009, Sun Yat-sen University
PhD Chemistry, 2014, University of Alberta

Postdoctoral Training

2017, Bioengineering/Pathology, Massachusetts Institute of Technology



 

Zhao Biophotonics Laboratory
Carnegie Mellon University
202A Mellon Institute
Department of Biological Sciences
4400 Fifth Ave
Pittsburgh, PA 15213

Phone: (412) 268-8236
Fax: (412) 268-1809

E-mail: Link

Website: Link


 

Insights into the inner life of living cells: Exploring cellular biophysics by single-molecule methods

The group focuses on the application of techniques from the emerging field of super-resolution microscopy to study cell biology. By combining physical concepts of imaging, photo-manipulation of fluorophores and quantitative read-out analyses, we aim at a single-molecule description of cellular structures and processes.

 

 

 

 

 


 

Education

Diploma in Physics, Bonn University (2008)

PhD (Dr. rer. nat.), Applied Laser Physics and Laser Spectroscopy, Bielefeld University (2012)

 


Postdoctoral Training

Postdoc, Biotechnology and Biophysics, Würzburg University (2012-2013)

Postdoc, Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt (2013-2014)

Group Leader at the Department of Systems and Synthetic Microbiology, MPI Marburg (10/2014 - ??/2020)

Associate Professor in Biophysics, CMU 


 

Endesfelder lab – Single Molecule Biophysics
Department of Physics
Carnegie Mellon University
500 Forbes Avenue
Pittsburgh, PA 15213

e-mail: uendesfe@andrew.cmu.edu
website: www.endesfelder-lab.org

 




 

Photo of Faculty MemberOur laboratory is interested in the fundamental question of how the cell controls the morphology and structure of its membranes. To this end, we are particularly interested in understanding endosomal sorting and the molecular mechanisms of endosomal membrane remodeling. Remodeling is performed by members of several protein families, including the SNX-BAR proteins and the dynamin-related proteins (DRPs). SNX-BAR and DRP mutations are both associated with health challenges, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

We use structural and biophysical approaches, supplemented with in vivo and high throughput genetic studies in the model organism S. cerevisiae. Recently, we used cryo-electron microscopy and X-ray crystallography, combined with live cell imaging and functional cell biological approaches, to characterize a retromer-dependent SNX-BAR involved in retrograde trafficking from the endosome as well as a DRP involved in endosomal membrane remodeling. In both cases, the structures we generated provided novel insights into the regulation of their function by self-assembly.

Our current work aims to understand how various SNX-BAR complexes are regulated and how they engage with their respective cargoes and binding partners, including members of the DRP family.

 


 

Education



Postdoctoral Training




 

Department of Cell Biology
University of Pittsburgh
3500 Terrace Street
Pittsburgh, PA 15261




Structural biology, pharmacology and signaling of G protein-coupled receptors (GPCRs) and drug development

My group studies structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) as important cell membrane-embedded receptors. GPCR family has over 700 members. They transduce signals from extracellular signaling molecules to intracellular effectors through conformational changes within the receptors to mediate and regulate a broad spectrum of physiological and pathological processes. GPCRs have been heavily investigated in the pharmaceutical industry, and they constitute 30-40% of current drug targets. My lab utilizes structural biology approaches including X-ray crystallography and cryo-electron microscopy (cryo-EM) and functional studies including ligand-binding assays and cellular signaling assays to explore the molecular mechanisms underlying the signal transduction of GPCRs. Currently, we focus on two groups of GPCRs, the chemotactic GPCRs involved in inflammatory diseases and the neurotransmitter GPCRs involved in neurological and psychiatric disorders. In addition, we also develop new GPCR antibodies as novel therapeutic candidates through combinatorial biology approaches such as yeast display.

 

 

 

 

 


 

Education

BS       2003, University of Science and Technology of China

PhD    2008, University of Science and Technology of China

 


Postdoctoral Training

2008-2014, Dr. Brian Kobilka's group, School of Medicine, Stanford University


 

Cheng Zhang
Department of Pharmacology and Chemical Biology
School of Medicine, University of Pittsburgh
W1311 BST
203 Lothrop St
Pittsburgh, PA15261

Website: https://www.czhanglab.org/

Phone: 412-383-8044
Email: chengzh@pitt.edu