Bacterial Bubbles blow away the bugs

 

There’s no shame in not knowing the names of every bacteria, there are billions if not trillions of different bacterial species. The number that are pathogenic in humans is significantly lower – probably in the high hundreds. One review estimates that there are 1,400 known species of human pathogens (including viruses and parasites). So, it is still ok to not have heard of all of them.

One that probably passes under the radar of many people is Acinetobacter baumannii, not least because it is an absolute nightmare to spell. It is a gram-negative opportunistic pathogen. Most cases of A. baumannii infection are hospital acquired, often catheter or ventilator associated. There are approximately 1 million A. baumannii infections annually and it is associated with a nearly 35% mortality rate. The most pressing problem associated with A. baumannii is antibiotic resistance; it is extremely drug resistant – with nearly half of the infections resistant to the last line antibiotic carbapenem. In fact Acinetobacter is the A in ESKAPE (the priority list of the most important antibiotic resistant bacteria).

Since it is so drug resistant, other strategies are needed to control it. One of which might be vaccines. In our recent study - Intranasal immunization with outer membrane vesicles (OMV) protects against airway colonization and systemic infection with Acinetobacter baumannii we developed a novel vaccine against this important pathogen. The approach we used was to manipulate a product of the bacteria itself to generate protection. A. baumannii produces little bubbles of lipids and proteins called outer membrane vesicles (OMVs). Bacteria use these OMV to communicate with each other and potentially help them better infect us. However, they also contain lots of different bacterial antigens, some of which are potentially protective. The highly effective vaccine against Meningitis B (Bexsero made by GSK) contains OMV.

In our study, we isolated OMV from clinical isolates of A. baumannii. Using clinically derived strains was important – as these are probably closer to the ones in circulation, than the ones used in many studies from older varieties. To test whether the OMV worked, we developed new models of infection using the same strains. We showed the recent clinical isolates were more pathogenic than the standard lab strain. The clinical isolates were able to escape from the lungs into the blood and appeared to stably colonise the upper airways for at least 7 days after the initial infection.

Our first studies tested injecting the vaccine into the muscle – as this is the most common route of vaccination used. OMV injected this way did give a good immune response – leading to the induction of antibodies. However, the immunity raised following this route of immunisation was not very protective against subsequent infection. When area of interest in the vaccine field has been mucosal vaccination – delivering vaccines to the site of infection, in this case the nose and lungs. When Dr Sophie Higham (lead author on the paper) immunised via the nose, protection was significantly improved with a dramatic reduction in bacterial load following infection.

This work shows two things – OMV can be very effective vaccine candidates against bacterial infections and that immunising in the site of infection can be beneficial. The next step is to look how to scale up for human studies.

Utopia is other people

What is the most important part of a Utopian institute?

The simple answer is people.

The complex answer is also people.

There is an extraordinary distance between these two answers.

In the simple answer above, although it says people actually means Principal Investigators (PIs), the big scientists – and their big egos. It finds beautiful, oak-lined common rooms for them to drink vintage port from antique glassware whilst sharing ideas, before returning to their perfectly stocked labs where their teams are grinding out data to answer their next big question. In the background faceless individuals settle accounts, assess risks and empty bins. In this model science does gets done. But the question is who benefits and would actually find it Utopian?

The complex answer is that a Utopian institute is for all the people who work there and delivering science for the benefit of everyone. Whilst the outputs are critical, I am going to focus on the people side – an institute where everyone who works there feels they are part of the Utopia. The first consideration is that there is no hierarchy; everyone is valued, everyone contributes, everyone wins. Easy to say, complex to deliver: it needs a rethink about how we do science work.

This flatter, more egalitarian structure doesn’t mean different people don’t have different roles. Lab heads will set direction, train and develop early career researchers. Whilst research staff will spend their time doing experiments (and thinking about them), they will be empowered to have ideas and contribute to the direction of the project. Professional, Technical and Operational staff (PTO) will enable the science as an integral part of the team. Each person working at this Utopian institute would spend their time constructively, supporting the mission to do excellent science for the benefit of all and in so doing grow as a person. Growth doesn’t have to be constrained to in work, external interests will be celebrated. Flexibility will be encouraged – both in terms of working hours and working location.

All of which is easy to write, and since this is a Utopian vision reaching for the sky is not unreasonable. And since institutes are currently made up of people, what is stopping us?

A major hurdle is the existing research science career structure. Having lab heads immediately speaks to there being a hierarchy. By the nature of things, there will be some people who are more established than others. And as people grow in their career, it is not uncommon to want to progress (in salary at least), but also develop a leadership role. And there is an additional driver – the desire to lead one’s own research program. This is important, for scientific progress there needs to be direction and a program of work. One approach is to consider the trade-off between responsibility, seniority and freedom; later stage career staff will have more responsibility and this will be reflected in a degree of seniority – earlier career staff will have more freedom. One of the benefits of a flatter structure is that it would take away the dilemma about long-term postdocs. If someone is happy in their role, they could stay in that role, because they are valued for the skills and knowledge they bring without the pressure for ‘independence’. Experience and knowledge can and should be celebrated, as long as it is passed on. In the end, clustering of programs of work under the leadership of a single person will deliver the best science, but the leaders should not be placed upon pedestals and should be seen as enablers. Going Diva free is a first significant step to a Utopian institute.

One way to achieve Utopia is to remove sources of friction. Not forgiving it, but some of the diva behaviour comes about due to frustration with systems and processes. In my Utopia, the IT and other underpinning systems will work seamlessly minimising friction, allowing everyone to do their main role: letting HR support and train staff, researchers research and everyone to process their expenses as easily as paying a credit card bill.

I strongly believe that if you get the people right, the science will follow, but there is some infrastructure that would definitely enhance the Utopian experience. In house expertise and capability to deliver specific techniques (in my case as a biomedical scientist that includes imaging, sequencing and flow cytometry). As with the open research, these teams will also be integrated into the greater whole – providing a service, but collaboratively. A common stock of shared reagents and consumables wouldn’t hurt. Funding is a tricky question, some form of competition is important in refining ideas, but acquisition of funding shouldn’t take up more time and resources than it delivers.

There are also physical design elements to the building itself to ensure integration. The best approach is a hub and spoke model, with individual functions requiring quiet reflection at the end of the spokes and getting more collaborative as you approach the centre. This means individual offices at the end of the spokes, with labs along the corridors and meeting/ communal spaces in the hub. The entrance is via the hub to ensure random interactions between staff occur. The communal spaces need to have spaces for big meetings, but also smaller pods for discussion. The aim is to enable free mixing, the kind that leads to collaboration and discussion. And of course any Utopia would have a subsidised creche, decent transport links, places to park bikes and showers. Last but not least, a true Utopia has a nap room.

The final part is cultural enabling and contains my only non-negotiable element. The provision of tea (and coffee if you insist) and set times to drink it. And not just tea, but good quality tea, milk (that you don’t have to spend 20 minutes hunting down) and mugs of the right size (and thickness). Given the complexities of the rest of what I have proposed, this at least seems achievable.

This a competition entry about Utopian science research institutes. It didn't win sadly, but I stand by what it says - people matter