8 min

Finding out why harmless nasal bacteria attack the brain

The bacterium Neisseria meningitidis is normally content to remain in the nose. But sometimes it enters the bloodstream and causes life-threatening meningitis. Edmund Loh is trying to find the answer to why this happens by studying small RNA molecules in the bacterium. He hopes his research will lead to new treatment strategies.

Edmund Loh

PhD Molecular Biology

Wallenberg Academy Fellow 2014

Institution:
Karolinska Institutet

Research field:
Examining the mechanisms behind meningitis in studies of new regulatory RNAs.

Edmund Loh has with him a beautiful small microscope from 1898, a find from an internet auction.

“I was given a similar one as a child. I remember how I went out in the garden looking for insects to study. My biology teacher, who had trained as a doctor, motivated me to become a researcher. She always said it was good to be curious, not to always believe what other people tell you, but to find out yourself how things work.”

Edmund Loh grew up in Kuala Lumpur, Malaysia, and went on to study biomedicine in Britain. Now he is studying why the bacterium Neisseria meningitidis, which is usually harmless, can in some cases penetrate the nasal membranes and cause meningitis.

“It’s a serious disease, contracted by about 100 people a year in Sweden, mainly infants. It can cause death within a couple of hours after the first symptoms appear if the patient is not given antibiotics. Even then, one in ten dies.”

Small RNAs

About 10-15 percent of people have these bacteria in their nose. The mystery Edmund Loh is trying to solve is why some people develop the disease while others do not.

“Sometimes the bacterium goes crazy, but we don’t know why. It makes its way into the bloodstream and attacks the brain. I want to know how, while it’s still in the nose, the bacterium knows what to do, and what makes it turn nasty.”

One way of understanding bacterial behavior is to study the proteins present on their surface. Protein production itself is determined by the DNA in the genes. Edmund Loh’s research is concentrating on RNAs, however, the step between DNA and protein.

“Proteins interact with the body. If we want to know what triggers protein production, we have to study RNAs. I am studying small regulatory RNAs, which do not code protein, but can bind to other RNAs and regulate other activities in the cell.”

Collaboration with Umeå

Edmund Loh’s interest in small RNAs was kindled at Umeå University, where he was admitted to a biomedical graduate school in 2003, and where he later obtained his PhD in molecular biology.

“Some 10-15 years ago many people thought these small RNA molecules were junk. My supervisor, Professor Jörgen Johansson, was one of the few researchers to realize their importance early on.”

Edmund Loh left Umeå to take up a postdoctoral position at Oxford University. He returned to Sweden in 2014, and has since then been building his own research team at Karolinska Institutet. He continues to collaborate closely with the Umeå researchers.

“Curiosity is an essential ingredient for success in research. You have to think outside the box. Without security you are less inventive and tend to play safe. The security provided by the funding from the Foundation makes it easier for me to be curious.”

In his earlier studies together with collaborators from Insitut Pasteur, Paris, Edmund Loh has succeeded in mapping small regulatory RNA in other pathogenic bacteria. With the help of funding from the Knut and Alice Wallenberg Foundation he is now looking for new small RNAs that may explain the transformation of Neisseria meningitidis. Eventually they may lead to new treatment methods for meningitis.

“The idea is not to kill the bacteria; the aim is to disarm them so that antibiotics can do their job.”

Special lab

For the time being, the work being done by Edmund Loh and his team does not require any hi-tech equipment. Hence the classic microscope he symbolically has brought with him.

“Believe it or not, but most of the technology we are currently using to discover how small RNAs work was actually developed in the 1950’s and 60’s.”

But working on Neisseria meningitidis, which is an aerosol-borne bacterium, requires a specially designed laboratory with a negative air flow, i.e. where the air is extracted. Otherwise there would be a great risk of infection. Researchers in the lab work under a lab hood and attempt to simulate the environment that the bacteria experience in the nose, e.g. different temperatures.

“One thing I studied in Oxford was how small RNAs in the bacterium sensed differences in temperature. Our findings were published in Nature in 2013.”

Influenza causes a local inflammation and a higher temperature in the nose. One theory is that Neisseria meningitidis then begins to produce proteins as protecting agents, since they believe that immune cells are coming to kill them. If the bacteria then end up in the blood and reach the brain, perhaps when someone blows his nose and small capillaries burst, the bacteria are already armed, and the immune cells there do not stand a chance. Edmund Loh is passionate as he explains:

“We know from statistics that the curve for influenza in particular, which often comes in waves during winter season, is mirrored by that for meningitis.”

Edmund Loh and his team are now trying to find more small RNAs that sense different things in the nose. A project in collaboration with researchers at Oxford has recently revealed that salt renders the bacteria less inclined to change.

“We don’t fully know what this means yet, but it’s really fascinating. When we understand more about these various mechanisms involved, we plan to examine samples from people who are carriers of this bacterium, and compare those who developed meningitis with those who did not.”

Text Susanne Rosén
Translation Maxwell Arding
​Photo Magnus Bergström