Breaking Down Walls
To truly understand the intricacies of pathogenic bacteria, we need to combine “pure” and translational research.
Danny Ward | | Opinion
Research science is composed of two branches. “Pure” or fundamental science seeks to advance our knowledge and understanding of the unknown. Applied science attempts to translate this knowledge into a developed product. In short, pure science builds a foundation of knowledge that can fuel applied research.
Without a deepening understanding of complex biological systems, we are greatly limited by the applications that we can develop from them. Think of it like trying to build a house: pure science research equates to learning a construction technique (or, perhaps closer to the truth, realizing that bricks exist), whereas applied science is the building itself. If we know how to lay bricks, we might get something that resembles a wall – but what about the roof, the electricity supply, plumbing, doors, windows…? Only when we understand multiple construction techniques (and are aware of all essential materials) are we able to build something more complete – and more useful.
I spend my time investigating complex unknown biological problems in an attempt to understand them better – pure science. At this stage, there is no direct application. And that is a deliberate decision that helps avoid swaying the research in any particular direction. Unlocking new knowledge could lead us to more innovative translational developments down the line; after all, the best discoveries are often the ones you aren’t looking for! Specifically, I am trying to better understand how certain bacteria can infect their hosts, causing disease. To do this, I work with the model organism Pseudomonas. We’re hoping to learn a great deal more from this species, but – crucially – be able to apply our findings to other similar species.
Pseudomonas targets many species in both the plant and animal kingdoms, using a type III secretion system to compromise the host – a system we don’t (yet) fully understand. What do we know so far? The type III secretion system is incredibly energy and resource intensive. Attached to the base of a needle structure, which the bacteria uses to infect its host, is a protein that acts like a tiny biological motor, capable of driving the system. This protein – an ATPase – helps scavenge the host’s ATP resources to power the system. The “motor” pumps out effector proteins into the target host cell, which drive changes that promote further bacterial colonization and disease progression. One hypothesis is that the bacteria controls the ATPase using a signalling molecule – cyclic-di-GMP. We’re using a variety of experimental techniques in molecular biology, biochemistry, and structural biology to improve our collective knowledge of this system.
I believe our work is incredibly important, because Pseudomonas is a major issue, both in healthcare and in agriculture. It often forms aggressive, difficult to treat infections in hospitals and, with growing antimicrobial resistance (AMR), the problem will only continue to worsen. And so, although my work focuses on a better understanding of the mechanism of infection, in the future it could inform translational research and development. By better understanding the type III secretion system and how bacteria are able to control it, we could develop control methods of our own. Could we develop medicinal drugs that are capable of targeting or mimicking regulatory molecules and, in so doing, hijack the bacteria’s infection machinery and shut it down? But what if we don’t fully understand the system? We may end up with a pile of bricks, possibly a wall… or perhaps a house of straw – with AMR being the big bad wolf!
I believe that continued investment is needed across the science spectrum; we cannot neglect pure science – especially if it is connected (even remotely) to the biggest public health burdens of our age. Likewise, funding of translational research initiatives is also essential – it connects my work to the real world. Doesn’t it typically take many skilled hands to build a house that will last many lifetimes?