Nicole Zitzmann
Targeting viral morphogenesis
Co-workers: Constantina Fotinou, Stephanie Pollock, Bevin Gangadharan, Stephen Woodhouse, Joanna Miller, Dimitri Lavillette, Sally Latham, Sam Cooper, Manisha Bapat, Melanie Beer, Ben Oestringer, Drew Sayce, Emma Dixon, Kelly Skelton, JL Kiappes, Simon Spiro
Aim of research
Hepatitis B virus (HBV), Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and dengue virus collectively infect more than 550 million people worldwide. We are developing antiviral therapies and methods of drug delivery to combat these viruses.
Morphogenesis inhibitors
The morphogenesis and pathogenicity of HBV, HCV, and HIV and dengue virus depend on the proper folding of viral envelope glycoproteins, cellular lipid metabolism and ion channels. We are developing iminosugar derivatives (monosaccharide mimics) and liposomes that interfere with one or more of these targets and which form the centre of our investigations. The antiviral properties of iminosugars have been validated for all four viruses and are being optimised to succeed in clinical settings.
Structure
We are studying the largely unknown structure, function, and location of the HCV p7 ion channel, a key target for drug development.
Viral proteomics
We use proteomics to investigate the biology of viral glycoproteins, virus-induced cell signaling pathways, virus-host interactions, lipid droplets and viral entry and its inhibition. Proteomics is also used to investigate the effects of HBV and HCV infection on the human serum proteome, and to allow earlier detection of newly identified serum markers for liver fibrosis and hepatocellular carcinoma
Publications
- Pollock S., R. Antrobus, L. Newton, B. Kampa, J. Rossa, S. Latham, N.B. Nichita, R.A. Dwek, and N. Zitzmann, Uptake and trafficking of liposomes to the endoplasmic reticulum. FASEB J., 2010. Jan 22 [Epub ahead of print]
- Luik P., C. Chew, J. Aittoniemi, J. Chang, P. Wentworth Jr, R.A. Dwek, P.C. Biggin, C. Venien-Bryan, and N. Zitzmann, The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy. Proc Natl Acad Sci USA, 2009. 106 (31): 12712-6
- Narayan, R., B. Gangadharan, O. Hantz, R. Antrobus, A. Garcia, R.A. Dwek, and N. Zitzmann, Proteomic analysis of HepaRG cells: a novel cell line that supports hepatitis B virus infection. J Proteome Res, 2009. 8 (1): p. 118-122
- Pollock, S., R.A. Dwek, D.R. Burton, and N. Zitzmann, N-Butyldeoxynojirimycin is a broadly effective anti-HIV therapy significantly enhanced by targeted liposome delivery. Aids, 2008. 22 (15): p. 1961-1969
- Scanlan, C.N., J. Offer, N. Zitzmann, and R.A. Dwek, Exploiting the defensive sugars of HIV-1 for drug and vaccine design. Nature, 2007. 446 (7139): p. 1038-1045
More Publications...
Research Images
Figure 1: Liposomes are lipid-based nanoparticles that can be used for delivery of small molecules inside the cell. A human DAPI- (blue nuclei) and fluorescein- (green ER membranes) stained hepatoma cell line was incubated with rhodamine-labeled pH-sensitive (top panel) or ER targeting (bottom panel) liposomes (red) and analysed by confocal fluorescent microscopy, showing co-localisation of liposomal lipids and the ER membrane in bottom panel only
Figure 2: An artistic view of simulated p7 monomers fitted into the hexameric EM volume. Atomistic models of p7 monomers were fitted into the EM density with their C- and N-termini oriented towards the petal tips
Contact: nicole.zitzmann@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: Enquiries with CV welcome