Biochemistry and bioinformatics

Overview

The group led by Dr Andreas Kukol uses methods of computational/physical biochemistry and bioinformatics in order to understand structure and function of proteins in health and disease.

Structural biology and bioinformatics of viruses

The influenza virus is a permanent threat to human health causing epidemics every year and less frequently devastating pandemics that have killed in the past up to 40 million people (Spanish Flu 1918/1919).  

While the recent H1N1 pandemic (Swine Flu) was rather mild, the avian H5N1-type virus has a much higher mortality rate. We have been looking at the structure of traditional drug target proteins and more recently began to investigate internal virus proteins as novel drug targets.  

Additionally, we are interested in the SARS-coronavirus, the HIV-virus and the dengue virus.

Structure and function of membrane proteins

Membrane proteins comprise 30% or more of cellular proteins. Many of them form receptors which control important intracellular functions as diverse as electric excitation or gene activation.

Even lipid-enveloped viruses contain membrane proteins important for the viral life cycle. Given the high abundance and biomedical importance, the paucity of high-resolution structures of membrane proteins is in stark contrast to the number of soluble protein structures.

This emphasises the need for more structural and functional information about membrane proteins. Recent projects involved new methodological developments in computer simulation as well as the study of systems relevant to cancer, heart disease and obesity.  

A particular topic of interest is the regulation of the cardiac sodium-pump by phospholemman (FXYD1). Phospholemman has been postulated as a new drug target for the treatment of heart failure.

There are close links with the Cardio-vascular Pathologies Group and the TRP Ion Channels Group.

Biosensor-arrays

Arrays of biosensors often utilise fluorescence labelling of the analyte in order to detect binding of the analyte to a probe.

The fluorescent label may interfere with the detection process and additionally requires expensive and bulky detection equipment.  

Our research is directed at biosensor-arrays that have minimal equipment requirements.

We envisage application of such sensors for the detection of pathogens in routine hospital labs, the doctors surgery or even in the open field.  

Applications for influenza virus gene sequences and Mycobacterium tuberculosis are investigated. There are close links with the Biotechnology and Molecular Biology Group.

Methods and equipment

• High-performance computer cluster (640+ CPU-cores) running GROMACS, AutoDock, AutoDock Vina, Gemdock, Modeller.
• Quad-core and hexa-core LINUX workstations.     
• Fluorescence Spectroscopy.       
• Fourier-transform infrared spectrometer (FTIR) with facilities for protein analysis (PROTEUS®), attenuated total reflection (ATR, 25 reflections and Smart iTR® with diamond crystal), specular reflectance, diffuse reflectance, DLaTGS detector, liquid nitrogen cooled MCT-A detector.
• Standard biochemistry/molecular biology lab facilities.

More details, downloads and current job opportunities can be found at the Research Group Page.