The Göran Gustafsson Prize, a total of SEK 33 million, is now awarded to five young researchers from Umeå, Lund, Uppsala, Gothenburg and Stockholm. The prize is granted to young researchers in medicine, molecular biology, chemistry, physics and mathematics. The five researchers are at the forefront of their field. With the help of the grant they will have the opportunity to focus on their research. Lund University researcher Vasili Hauryliuks will receive a prize sum of SEK 6.6 million, a grant spread over three years.
Congratulations – what does this prize mean for you?
It is a fantastic recognition of the work that people in our lab have been doing for many years: first on protein synthesis, antibiotics targeting it and antibiotic resistance mechanisms that counter the antibiotics – and more recently, on bacterial viruses, bacteriophages. The visibility that the prize brings is very welcome, since I believe these are socially important research topics.
You are interested in bacteriophages; can you describe what they are?
Just like us humans are infected by viruses, bacteria are also infected by viruses. These are called bacteriophages, or simply phages. The term is derived from the Greek 'phagein', meaning 'to eat'. They are very picky eaters – a specific type of phage will usually attack only a specific type of bacteria, often just a specific strain. This makes them fantastic as a precision tool when you want to specifically eradicate a bacterial pathogen. While antibiotics would wipe out all sensitive bacteria, both good and bad, a treatment with phages allows for a much more specific intervention, sparing the good bacteria. While human viruses commonly look like spiky balls, a typical phage looks like lunar lander. The reason being is that phages need to 'land' on a bacterium and then inject their DNA inside it, acting as a syringe.
What is going on in bacteriophage research?
Many things! Fundamental phage research is advancing at lightning speed. One exciting direction is antiphage immune systems that defend the bacteria against the infecting virus. Numerous new microbial immune systems are being discovered and characterized, and therefore subsequently exploited for medical and biotechnological applications. With the advent of AlphaFold – an artificial intelligence program for predicting 3D protein structures from protein amino acid sequence – we now can make educated guesses regarding what the individual bacterial and phage proteins do and then ask the right questions experimentally. Applications of phages are rapidly gaining ground. In medicine they are already used as antibacterial agents to treat severe antibiotic-resistant infections. In agriculture, animal husbandry and food production they are also used to treat bacterial infections or applied to prevent the spoilage of produce by bacteria. These applications require understanding of antiphage immune systems: to work effectively phages should be able to overcome the bacterial countermeasures; one can think about it as one would about antibiotics and antibiotic resistance.
Why are you excited about bacteriophages?
Phages are extremely diverse and evolutionarily creative. When you work in this field you are constantly bombarded with jaw-dropping discoveries made by research teams all over the world – and sometimes you make a fun discovery yourself! The promise of new molecular tools is very exciting. Phage research has already given many crucial molecular biology tools. Restriction enzymes that are naturally used by bacteria to recognise and cut the invading phage DNA were exploited for recombinant DNA technology, that is for cutting and stitching DNA sequences together. Phage-derived Cre-Lox recombination system and the CRISPR-Cas9 antiphage defence system are used for genomic manipulation of mammalian cells. An RNA polymerase from the phage called T7 is widely used for recombinant protein production, that is for making bacteria specifically produce the protein of interest. The possibility of discovering the ‘new CRISPR’ is exciting!
Where will we be in this research in 5-10 years from now?
In our specific field of antiphage immune systems there is an ongoing shift from discovery to understanding how they work on the molecular level: how these defence systems sense the invading phage, how they stop its propagation. There will be more and more of this. We will gain a holistic understanding of antiphage immunity, comprised of different individual antiphage countermeasures and gain an understanding akin to what we have of the human immune system. Genetic manipulation of phages will progress dramatically, and we will see ‘designer phages’ aimed to target specific bacterial pathogens, precisely engineered to overcome their defences.
What would you like to achieve/investigate further in your research on bacteriophages?
Our specific fundamental research aims to follow up the many leads we have now on a mechanistic level. We have discovered numerous antiphage systems, but now we need to figure out how they work and see how we can apply them biotechnologically. Our team strives to put Lund on the world map of phage research. While the individual success of our team is important, it is equally crucial to build networks and to form a hub for phage excellence. Connecting basic research to clinical practice is essential. Establishment of phage therapy centres for treatment of antibiotic resistant infections that bring together molecular microbiologists and clinicians is a proven model in other countries such as Belgium, UK and France. I would like to see that happening in Lund.