Molecular mechanism of amyloid fibrils in health and disease



The aim of my Lab is to understand molecular mechanisms of amyloid fibrils in health and disease. Amyloid fibrils are known for causing pathological neurodegenerative diseases such as Alzheimer’s (via Ab) or Parkinson’s (via aS), but also have specific biological functions in living organisms, functional amyloids. My research focuses on two main areas: neurodegenerative amyloid proteins and biofilm forming bacterial functional amyloids, a major cause of persistent infections and an antimicrobial resistance (AMR) target. We aim to determine atomic resolution structures and molecular dynamics information, for better understanding of amyloid formation and biofilms. This will pave the way towards future treatments against neurodegeneration, bacterial infections, and their antimicrobial resistance.

We use modern solid state NMR (ssNMR) spectroscopy to study these insoluble/non-crystalline proteins. We develop novel NMR methods to push the limits of the state of the art and apply them to understand molecular details and mechanisms of amyloid fibrils. ssNMR has made a remarkable progress in the last decade to become a high-resolution and -sensitivity method due to advances in sample preparation, hardware, novel methods such as proton-detection and hyperpolarization. These allow studies of these difficult proteins not only in vitro, but also in their complex native in vivo environment. Akbey Lab also like to combine NMR with other exciting structural biology tools.

 


Education

Undergraduate

1999-2005:       B.Sc. in Chemistry, Bilkent University, Ankara, Turkey

Graduate

2005-2008:       Ph.D. in Solid-state NMR, Max Planck Institute, Mainz, Germany

Postgraduate

2009-2015:       Leibniz Institute for Molecular Pharmacology, Berlin, Germany

2015-2018:       Aarhus University, Aarhus, Denmark
2018-2019:       Forschung Zentrum Julich, Julich, Germany
2020-2021:       Weizmann Institute of Science, Rehovot, Israel
2021:                Radboud University of Science, Nijmegen, The Netherlands




Asst. Prof. Ümit Akbey
University of Pittsburgh, Department of Structural Biology, School of Medicine
2044 Biomedical Science Tower 3
3501 5th Ave. Pittsburgh, PA, 15261, United States.
Office: +1 412 383 9896
E-mail: umitakbey@pitt.edu

Phone: (412) 383-9896
Fax: (412) 648-9008

E-mail: umitakbey@pitt.edu

Visit website

 


 

Structure and function of cellular machinery in human parasites


 

My lab is dedicated to the experimental and computational application of cryo-ET for structural determination of biological macromolecules or biological machinery in single-celled parasites that cause important human diseases. I am particularly interested in understanding the molecules transportation, organelle biogenesis and their regulations in the invasion process of the malaria parasites (or related apicomplexan parasites) and the migration of Trypanosoma brucei that causes African sleeping sickness in humans and Nagano in cattle. Our research is to visualize the organization of cellular structures and their coordination in 3D spatial organization through a multi-scale imaging platform ranging from microns to sub-nanometers, to elucidate the molecular and structure functions that drive cell migration or invasion. Crucially, the novel cryo-ET analysis developed will also broadly enable the study of molecular machines in other complex biological contexts.

 

 

 

 


Education

B.S. 2008, Wuhan University, Wuhan, China
Ph.D. 2014, National University of Singapore, Singapore

Postdoctoral Training

2014-2016, Mechanobiology Institute, Singapore
2016-2017, Baylor College of Medicine, Houston, United States
2017-2021, Stanford University, Stanford, United States


Stella Sun
Department of Structural Biology
University of Pittsburgh
2050 Biomedical Science Tower 3
3501 5th Ave.
Pittsburgh, PA 15260

Phone: (412) 648-9959
Fax: (412) 648-9008

E-mail: stellasun@pitt.edu

Visit website

 


 

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) 648-4077
Fax: (412) 648-9008

E-mail: coleman1@pitt.edu

Website link: coming soon

 


 

Synthetic biology approaches to engineer immune cells.


 

We use synthetic biology approaches to genetically reprogram immune cells to treat disease. Immune cells are an ideal chassis for therapeutic intervention as they are involved in the prevention or pathology of nearly every major disease, they can be genetically manipulated, and they have the capability of migrating to and affecting most locations in the body. Our major scientific goal is to overcome current barriers to successful adoptive T cell therapy, especially for solid tumors, including immune inhibitory signals of the disease micro-environment, cell-intrinsic limits to T cell persistence and function, and developing new antigen targeting strategies to avoid toxicities and cancer relapse. One key technology that we are developing is “universal” cell receptor systems that can be targeted to any cell surface antigen of interest by co-administered antibody adaptors - allowing the same engineered T cells to be used to target multiple antigens in a patient or across patients. To further enhance universal receptor specificity, we are creating conditional ON and OFF-switch adaptor molecules. Another major focus of the lab is on re-wiring immune cell signaling pathways to respond to novel inputs and the engineering of artificial cell-cell communication. Our standard experimental system for developing these technologies is viral engineering of primary human T cells followed by functional characterization in vitro by flow cytometry and live cell high-content fluorescence imaging and in vivo testing in pre-clinical humanized tumor xenograft mouse models.

 


Education

Sc.B.  2007, Brown University
Ph.D.  2013, Harvard University

Postdoctoral Training

2013-2019, University of Pittsburgh


Jason Lohmueller
Department of Surgery
Division of Surgical Oncology
University of Pittsburgh
Hillman Cancer Research Pavilion, Suite 1.4
5117 Centre Avenue
Pittsburgh, PA 15213

E-mail: jasonloh@pitt.edu

Visit website

 


 

 

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