News - Page 4 of 5 - Ben Libberton

I’m happy to say that the Liverpool team and I have published a paper in Infection and Immunity. I really enjoyed doing this work and I think I & I is a really good place for it. I hope people enjoy reading it.

The title is “Evidence that intraspecific trait variation among nasal bacteria can shape the distribution of Staphylococcus aureus”

Over the last decade or so, the various -omics fields have exploded. They have allowed us to see detail in biology that was previously impossible. In the field of Microbial Ecology, genomics has allowed for in depth research into microbial community composition which affects everything from human health to global warming. It’s very important!

Our work in this paper is very much a complement to the masses of information produced by genomic and metagenomic analyses. We found that differences in the traits possessed by bacteria found in the microbial communities of human noses were important for colonisation, irrespective of which particular species exhibited those traits. This is an important finding with respect to metagenomics which focusses solely on species identification within microbial communities. Identification is important but it doesn’t necessarily tell us what the organisms are doing or how they contribute to the community structure.

Here, we identify a trait (inhibition/toxin production) that we can measure across bacteria isolated from the noses of 60 healthy volunteers. We tested every strain that we isolated for the ability to inhibit S. aureus in an agar plate based assay. We found that communities that contained more inhibitory strains, were less likely to contain S. aureus. We also found that inhibitory subsets of species were significantly negatively associated with S. aureus when the species as a whole was not negatively associated. Our example shows that Micrococcus luteus is only negatively associated with S. aureus when you consider the inhibitory fraction. No previous papers have shown negative associations between S. aureus and M. luteus before. We believe this is because you would never see a negative association unless you look specifically at this inhibition phenotype.

While this study is relatively small and low throughput, it addresses the need to consider trait variation as well as genotypic variation when trying to understand microbial communities. With exciting new microfluidic technologies on the horizon, it will soon be possible to perform these kinds of assays on much larger microbial communities at a high throughput pace. Until then, we should take care to try to understand trait variation using the high throughput technologies that we have at our disposal. For example, it may be possible to infer traits by looking for toxin genes in metagenomic analyses or by looking for toxins in a parallel proteomic study.

If you’re interested in reading the paper, here is the link.

I’ve just finished preparing a half-day workshop on Scientific Communication for the Swedish Medical Nanoscience Center at the Karolinska Institute.

The workshop will focus on how we as scientists should approach promoting ourselves when we are looking for a job or research funding. This is quite a difficult topic as many of us cringe when we think of the idea of self-promotion. We automatically think of the sleazy salesperson which has nothing to do with our work in science. However, these days, being able to stand out from the crowd is more important than ever and with so many tools available (especially online) it can be difficult to know where to start.

In this workshop, I start with basic principles of how to communicate the value we offer to prospective employers and funding bodies, followed by strategies and tools to give ourselves the best exposure.

If you are interested in a similar workshop then please get in contact.

I have a new Postdoc position at the Karolinska Institute in Stockholm. Here I’ll be working with Agneta Richter-Dahlfors on the infection of indwelling medical devices. My aim is to understand the infection process, as well as develop novel strategies for treatment and detection.

The Karolinska Institute is one of the top-ranking clinical research institutes in the world where they decide who gets the Nobel Prize for Medicine each year. I’m really looking forward to the move and to applying my research directly to the hospital ward.

I will be working at the Swedish Medical Nanoscience Center in the Department of Neuroscience. I’ll be working alongside infection biologists and engineers making it a truly interdisciplinary project where I’ll hopefully also be able to lend my expertise in microbiology (especially with staphylococci).

Department of Chemistry at the University of Liverpool

I’m looking forward to start an interesting collaborative project between the chemistry and biology departments at the University of Liverpool to try and understand more about DNA lesions that lead to mutation and cancer. The project encompasses everything I love about interdisciplinary research, using novel synthesis methods in chemistry to adress a question that biologists have had for a long time. The answer to this question will hopefully lead to therapeutics and detection systems in the future.

During this project I’ll be looking at a specific type of DNA lesion known as 8-nitroguanine (8-nitroG). We know that it is the cause of mutation and cancer in humans but as yet we do not know exactly how.

8-nitroguanine is produced during inflammation and leads to cancer

Inflammation leads to reactive nitrogen species (RNS) being produced within human cells. These RNS (such as ⋅NO₂ and ONOO^– then react with nucleotides and change their chemical structure and biological properties. I’m going to be investigating the effect of RNS on guanine because it is the most susceptible to attack by these particular molecules.

8-NitroG can then be incorporated into the DNA strand. However it is very unstable, and can disassociate from the DNA strand very easily leaving an abasic site (“hole” in the DNA lacking a base) which is known to cause mutation.

Stabilising 8-NitroG

Due to its instability, the effect of 8-NitroG is very difficult to study. We can never be sure if we are measuring the effect of the lesion itself, or an abasic site left by the disassociation of 8-NitroG. Working with the chemistry department at the university of Liverpool (Prof. Rick Cosstick), we have synthesised a stable mimic of 8-NitroG which we can use to study the effect of this lesion when it is in the DNA strand. We can determine how DNA polymerases react when they encounter a lesion and this has already been characterised by the group (Bhamra et. al. 2012). They showed that the presence of stable 8-NitroG causes stalling of the DNA polymerase and preferential incorporation of an A residue (instead of a C) opposite the lesion. These experiments were all carried out in vitro, my role will be to investigate the properties of this lesion in vivo using bacteria as a model system.

In vivo characterisation of the 8-NitroG lesion

Using E. coli as a model for repair and replication, I will introduce the 8-NitroG lesion into the α-complementation portion of the LacZ gene. This will allow for phenotypic characterisation of the lesion before sequencing to determine to precise nature of any mutations that have taken place. This will also be done in DNA-repair deficient mutants.

References

Bhamra, I. et al. Base-pairing preferences, physicochemical properties and mutational behaviour of the DNA lesion 8-nitroguanine. Nucleic acids research 40, 11126–38 (2012).

Keith, B., Jozwiakowski, S. & Connolly, B. A plasmid-based lacZα gene assay for DNA polymerase fidelity measurement. Analytical biochemistry 433, 153–61 (2013).

Suzuki, N., Yasui, M., Geacintov, N., Shafirovich, V. & Shibutani, S. Miscoding events during DNA synthesis past the nitration-damaged base 8-nitroguanine. Biochemistry 44, 9238–45 (2005).

Sawa, T. & Ohshima, H. Nitrative DNA damage in inflammation and its possible role in carcinogenesis. Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society 14, 91–100 (2006).

Ohshima, H., Sawa, T. & Akaike, T. 8-nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species: formation, occurrence, and implications in inflammation and carcinogenesis. Antioxidants & redox signaling 8, 1033–1045 (2006).

Kawanishi, S. & Hiraku, Y. Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation. Antioxidants & redox signaling 8, 1047–1058 (2006).

It was great to be honoured at the Celebrating Success Awards at the University of Liverpool this year. We were nominated as a group in the “Excellence at Innovation” category for setting up and running a postgraduate society. Over several years we were responsible for a campaign of integration of PhD students across all facets of biological sciences within the university. We used a combination of training seminars, such as careers talks and Biotechnology YES workshops and social events to make sure that not only did new PhD students feel welcome into the department, but that the department as a whole felt more connected and able to help each other out with advice and collaborations.

Not only were we nominated, we won!

We won the prize at an evening hosted by the vice chancellor. It was great to see all our hard work being recongnised in such a prestigious awards ceremony. It goes to show how much the university values our efforts to integrate postgraduates within our institute, as well as use our time to do valuable community outreach and raise money for charitable causes.

Ben Libberton

New paper published in Infection and Immunity

Leading Communication Workshop at Swedish Medical Nanoscience Center

Moving to the Karolinska Institute in Stockholm

New Post-Doc working on DNA damage and repair