Dr Daniel Ungar
Senior Lecturer

Profile

Career

2016 -  Senior Lecturer Department of Biology, University of York
2007 - 2016 Lecturer Department of Biology, University of York
2000 - 2007 Post-doc Princeton University, USA
1999 PhD in Biochemistry MPI of Biophysics/University of Frankfurt, Germany
1995 MSc in Chemistry Eötvös Loránd University of Budapest, Hungary    

Research

Overview

 

The diversity of eukaryotic glycan structures is produced by a large number of Golgi localized glycosylation enzymes. The precise localization of these enzymes to different Golgi cisternae is essential for accurate glycan synthesis. We are interested in the vesicular transport processes that sort resident enzymes to their cisternal destinations. The main goal of our group is to characterize the molecular mechanisms of vesicle targeting and its influence on glycosylation homeostasis in the secretory pathway. For this we focus on the conserved-oligomeric-Golgi (COG) vesicle targeting complex, whose mutations have been found to cause congenital glycosylation disorders in humans. 

Recent discoveries

We have recently mapped the interactions between the eight mammalian COG subunits and members of other trafficking protein families, namely Rab GTPases, golgin type tethering proteins, SNAREs and the COPI vesicle coat. Detailed investigation of the interactions between COG, the golgin TMF and the Rabs Rab1 and Rab6 led us to propose a mechanism of Golgi-based vesicle tethering during which COG helps to reel in the vesicle tethered by TMF, assisted by the binding specificities of the two Rabs. In a parallel collaborative effort we have looked at the functional interplay between Golgi-SNAREs and COG, and found that the different halves of COG provide assembly platforms for cis and trans-Golgi SNARE complexes respectively. The protein interaction studies were complemented by the development of a cell-free vesicle tethering assay that we can use to investigate mechanistic details of COG-dependent as well as COG-independent congenital glycosylation disorder cases. We found that the Cog1-4 half (lobe A) of COG may be inhibiting the Cog5-8 (lobe B) half during trans-Golgi vesicle tethering.

  • Cottam NP, KM Wilson, BG Ng, C Körner, HH Freeze, D Ungar (2013) Dissecting functions of the conserved oligomeric Golgi tethering complex using a cell free assay. Traffic, DOI:10.1111/tra.12128.
  • Willett R, Kudlyk T, Pokrovskaya I, Schönherr R, Ungar D, Duden R, Lupalshin V (2013) COG complexes form spatial landmarks for distinct SNARE complexes. Nat. Commun., 4: 1553.
  • Miller VJ, P Sharma, TA Kudlyk, L Frost, AP Rofe, IJ Watson, R Duden, M Lowe, VV Lupashin, D Ungar (2013) Molecular insights into vesicle tethering at the Golgi by the Conserved Oligomeric Golgi (COG) complex and the golgin TMF. J. Biol. Chem., 288, 4229-4240.

Projects

Developing diagnostics for CDG

Funding body: Centre for Chronic Diseases and Disorders (C2D2)

Modelling of glycosylation in Cog1 dependent CDGs

Funding body: Discipline hopping internship of the C2D2

Research group(s)

StatusNameProject
PhD student Peter Fisher Modelling glycan biosynthesis
PhD student (joint with Paul Genever, Victor Chechik (Chem), Andrew Pratt (Phys)) Matthew Walker Design of Magnetic Nanoparticles for drug delivery
PDRA (joint with Nia Bryant) Agnieszka Urbanek

Enhancing the production of therapeutic antibodies through engineering of the secretory pathway

PDRA (joint with Nia Bryant) David Mentlak

Enhancing the production of therapeutic antibodies through engineering of the endoplasmic reticulum

Senior Technician (with Nia Bryant) Dimitrios Kioumourtzoglou

Enhancing the production of therapeutic antibodies

Available PhD research projects

Connecting vesicle targeting with SNARE complex assembly (2015-16)

The 2013 Nobel prize in Medicine was awarded for the discovery of the protein factors involved in intracellular vesicle transport. Vesicle transport is critical for processes such as neurotransmitter release or insulin regulated GLUT4 secretion, and therefore impacts on areas like neuroscience and diabetes. Yet the regulation of the final step of vesicle trafficking, the fusion of the two membranes is not well understood. It is well known that a SNARE complex that bridges the two membranes has to form to fuse these membranes, but how SNARE complex formation is regulated is an important open question. We would like to understand how the process of vesicle targeting regulates SNARE complex formation and thereby membrane fusion. During vesicle targeting the first contact between the vesicle and target membrane are made, and therefore this is a key site for vesicle trafficking specificity – where does a vesicle end up in the cell. Large multisubunit tethering complexes (MTCs) coordinate vesicle targeting throughout the cell, one working at the Golgi apparatus is the COG complex. COG is important for the sorting of Golgi-resident proteins, most notably glycosylation enzymes, but also Golgi SNAREs. COG is known to interact with several Golgi SNAREs, yet if this interaction is involved in regulating SNARE complex formation is not established. We will use biochemical SNARE assembly assays with purified COG to address this question. Mutant COG complexes will also be generated, which cannot bind SNAREs, and tested both in the biochemical assay and for their ability to alter sorting within the Golgi. Golgi sorting will be assessed by analyzing the glycosylation potential for cells using a mass spectrometric glycan profiling method. Thus this project will combine biochemical, cell biological, glycobiological and mass spectrometric methods for the analysis of an important cell biological problem.

Miller VJ, Ungar D (2012) Re’COG’nition at the Golgi. Traffic, 13, 891-897

Co directors - Nia Bryant

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Contact details

Dr Daniel Ungar
Senior Lecturer
Department of Biology (Area 9)
University of York
Heslington
York
YO10 5DD

Tel: 01904 328656

https://sites.google.com/a/york.ac.uk/ungar-lab/