#pokolenieNCN – Agata Starosta: We’re looking for skeleton keys in bacteria
The NCN Generation series brings together researchers whose work broadens our knowledge and shapes our lives – serving our health, the environment, technological progress and a better understanding of the world. The sixth episode features Dr hab. Agata Starosta, a molecular biologist and professor at the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences.
After spending well over a decade conducting research in Germany and the United Kingdom, she now leads a team studying the fundamental life processes of bacteria at the IBB PAS.
The weak points of bacteria
We tend to associate bacteria mainly with disease, yet most are harmless and many are positively indispensable. Bacteria build soil, clean up the environment and help produce food, while those living in our gut shape how we function. Science came to appreciate their beneficial role only relatively recently – through the discovery of probiotics in the 1960s and 1970s and, later, through microbiome sequencing.
Agata Starosta studies protein biosynthesis – a process fundamental to every living cell. She works with the hay bacillus (Bacillus subtilis) and looks for points at which bacteria differ from human cells. She describes these differences as ‘skeleton keys’: individual proteins that behave differently from their human counterparts can be used to design antibiotics that eliminate pathogens precisely when needed, while leaving beneficial bacteria untouched.
Her team is looking for similar mechanisms in Antarctic bacteria collected at the Arctowski Station, which is run by the IBB PAS. The station has been operating for almost fifty years, and the collection assembled there includes strains from places that no longer exist – melted glaciers, for example. They remain largely unstudied, and some of them could no longer be obtained today.
How her team rewrote the textbooks
At school we are taught that in bacteria transcription and translation are coupled – the ribosome reads the information from RNA immediately behind the polymerase transcribing it from DNA. This was regarded as a hallmark of bacteria, one that was meant to ensure fast and efficient protein production. Agata Starosta’s team has shown, however, that in the hay bacillus the two processes are not always coupled and can take place in different parts of the cell, much as they do in higher organisms. This allows the bacterium to regulate more precisely which proteins it makes and where – for instance, when it runs short of food or when stressors appear in its environment. One of the team’s hypotheses is that the hay bacillus may be a distant relative of eukaryotic cells.
From a weak point to a drug
Once a weak point has been identified, the team tests whether molecules from chemical libraries can bind to it and block the process in question – the starting point for work on a new drug. In one project, carried out in collaboration with a pharmaceutical company, the team’s basic research made it possible to identify molecules that went on to further development. The resulting drug is now on the market.
The search for further weak points has a practical purpose. The more antibiotics we use – in medicine, but also in agriculture, from where they find their way into water and soil – the stronger the pressure favouring resistant bacteria becomes. Today antibiotic resistance is responsible for more deaths each year than malaria and AIDS combined, and developing a new antibiotic takes around ten years – long enough for bacteria, in some cases, to learn how to cope with it. That is why new points of attack are constantly needed.
Selected statements
Bacteria rule us
When people talk about a ‘gut feeling’, the gut really does send us signals. Many of the signals that steer our lives and the way we function come precisely from bacteria.
An encounter with biology
My first encounter with biology came when, as a child, I developed tonsillitis that no antibiotic could clear. I was then given an antibiotic that was still in the clinical-trial phase. It was azithromycin, which I later worked on, among other things, during my doctorate. Somehow, things had come full circle.
What fascinates her
Translation itself is an absolutely fantastic and fascinating process. It is a mystery to me why it is so often overlooked, even though it is a fundamental process and one of the most important processes targeted by antibiotics.
What the NCN means to her
An NCN grant allowed my team to move to the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, where we could pursue every idea we had. NCN gives us that measure of stability. It lets us do what gives us enormous pleasure and, at the same time, change the way this biology is understood.
The #pokolenieNCN series consists of 15 conversations with 15 researchers to mark the 15th anniversary of the National Science Centre. Each conversation lasts 15 to 20 minutes. They are hosted by Anna Korzekwa-Józefowicz.
In earlier episodes, we spoke with Aleksandra Rutkowska, Michał Tomza, Małgorzata Kot, Karolina Ćwiek-Rogalska and Maciej Trusiak. In upcoming episodes, we will hear from Karolina Safarzyńska, Rafał Szabla and Maciej Grzybek. The episodes are released on NCN’s YouTube channel every third Thursday.
