Sweet solutions for detecting disease
In Bratislava, the team of Dr Ján Tkáč is developing the weapons to fight back in a cellular ‘cold war’ by using new early-detection technologies – helped by the first ERC grant awarded in Slovakia. Glycans are sugar molecules that carry the information human cells need to stay healthy and fight infections. Information rich, and with sophisticated storage and coding commands, they are a vital early-warning system for triggering an organism’s natural defensive systems at the first sign of attack. So it is not surprising that infectious pathogens such as bacteria and viruses, and cell-related diseases such as cancers, have developed subterfuges to bypass this first line of defence. For example, HIV viruses do this by cracking the glycan’s molecular code, and stealing its identity – allowing the pathogen to go unrecognised by cells until the infection is well advanced.
Based at the Institute of Chemistry in the Slovak Academy of Sciences, Ján Tkáč’s research combines glycomics – the study of sugars in organisms – with biochip sensors based on nanoparticles and nanotubes. The complexity of sugar molecules, he says, has so far held back the development of glycomics, but today it is one of the fastest developing scientific fields. “This is vital research as there is growing evidence of the importance of glycans in many aspects of cell physiology and pathology,” explains Dr Tkáč. “Here at the Institute we were very pleased with the ERC award because, after welcome EU investment for infrastructure, this five-year grant for ground-breaking research gives us the long-term stability we need to develop our team of young researchers and achieve real excellence in glycomics”. Dr Tkáč currently employs four PhD students and one post-doc in his research team with the support of his ERC grant.
Biochips for early warning
In the ELENA project, Ján Tkáč’s team is developing innovative biochips that can detect changes in ‘glycosylation’, of glycans attached to a protein or other organic molecules, and which can indicate diseases such as cancer. A typical ELENA biochip starts with a gold-plated glass substrate. Nanoparticles are then deposited on to the gold surface, followed by a layer of lectin (a glycan recognising protein). Finally, a layer of glycoprotein is deposited over the lectin after incubation with a sample. Interactions between the lectin and glycoprotein layers can then be detected by changes in the electrical resistivity of the biochip assembly. “The importance of the nanoparticles is their size,” explains Dr Tkáč, “they are small enough for us to study interactions at the cellular and molecular level and offer greatly improved detection limits.”
“Indeed, ELENA’s first nano-biochips are proving more sensitive by factors ranging from 1 million to a billion compared to state-of-the-art fluorescent biochips. We can catch diseases earlier on, with the possibility of treating them more effectively in the future,” he says. “And high sensitivity means the biochips can be small, which opens possibilities for in vivo measurements – with the prospect of putting the biochip into the patient. This technology offers much in the fight against diseases that disguise themselves well, such as various forms of cancers – making it difficult for our body’s cells to detect and combat it.”
As well as faster, more sensitive detection, ELENA also aims for nano-biochips that are more accurate. Current laboratory methods use ‘labels’ to help detect interactions – such as fluorescent dyes. But such ‘labels’ can influence the local environment and the properties of protein and glycan molecules – leading to false results in some cases. “By tracking interactions by measuring changes in electrical resistivity, our technology is ‘label free’. So we can preserve a much more natural way of interaction, closer to that in the organism, which will make our measurements and diagnoses not only faster and more sensitive but more accurate,” explains Dr Tkáč.
As regards the research environment in Slovakia, it is getting better due to presence of world class infrastructure, he says, and he believes that this, in combination with ERC grants, can reduce the brain-drain and attract highly-qualified people to do science in Slovakia.
Project details:Researcher (PI):Ján TkáčHost institution:Chemicky Ustav Slovenskej Akademievied, SlovakiaProject:Electrochemical LEctin and glycan biochips integrated with NAnostructures, (ELENA)ERC call:Starting Grant , ERC-2012-StG, panel LS9Max ERC funding:1,155,970 €Duration:Start date: 2013-01-01, End date: 2017-12-31