Poster at the 8th European Conference on Mathematical and Theoretical Biology

Dorota Herman is at the 8th European Conference on Mathematical and Theoretical Biology in Krakow this week where she is presenting a poster on her work. Poster abstract is below.

Dorota Herman, Chris Thomas and Dov Stekel

Evolutionary optimization of negative and co-operative autoregulation in RK2 plasmids

The central control operon of the RK2 plasmid is negatively and co-operatively autoregulated by dimers of two global plasmid regulators, KorA and KorB. Several roles for negative feedbacks in biosystems have been proposed by many researchers, and these roles include reduction of noise, increased robustness, speeding of response time and reducing burden on host. In this work, we seek to explain the evolutionary adaptation of the RK2 central control operon in terms of these proposed roles, using comparative analyses of the wild type system with a progression of simpler systems. We used a stochastic, multi-scale model that includes negative and co-operative gene autoregulation of the central control operon of the plasmid, plasmid replication and host cell growth and division. Keeping track of an RK2 plasmid line, we can observe the dynamics of protein abundance from entry of the plasmid into a naive host through to steady state. The comparative analyses between the regulation in models of the wild type central control operon and models with simpler, adequate architectures show a speed up of response time and a decrease in burden for the host, indicated by a decrease in the number of produced mRNAs. In comparison, minimal increased robustness and reduction of internal noise in steady state of bacterial growth phase were observed in these anayses. We conclude that possible reasons for evolution of the complex negative feedback regulation of the RK2 central control operon are the optimization of fast response times and reduced burden to host, and that it is unlikely that this regulatory system has evolved to reduced noise or increase robustness.

Editorial Board for Frontiers in Bioinformatics and Computational Biology

I have just accepted an invitation to join the editorial board for Frontiers in Bioinformatics and Computational Biology. This is an interesting, open access journal publishing articles across a very broad range of bioinformatics, systems biology, computational biology and related areas. I look forward to reading and reviewing some interesting articles!

Welcome to Dr Hiroki Takahashi

This week we welcome visiting scientist Dr Hiroki Takahashi from the Nara Institute of Science and Technology to our laboratory. Hiroki will be with us for 4 months. He writes:

I’m working in Nara Institute of Science and Technology in Japan as an assistant professor of Professor Kanaya laboratory. Now I’m visiting Dr. Dov Stekel laboratory for 4 months as part of a collaboration between the University of Nottingham, the Nara Institute of Science and Technology and Osaka University, funded by BBSRC/JST.

I graduated from Kyoto University for BS and then NAIST for MS and PhD. Until now, my research topic is omics data analysis, especially based on metabolomics approach for microbes. For example, please see the following sites.

http://amdorap.sourceforge.net/

http://www.liebertonline.com/doi/abs/10.1089/omi.2010.0074

In this stay, I’m going to study about mathematical modeling of zinc regulation system in E. coli. Through this theme, I really want to know what mathematical modeling can do or not and how it can work or not.

Transposon corn cob in my office

I have been packing my office today in preparation for the move to the new building. Most of the effort has gone into sorting out research papers. But among my things I found the corn cob that I found some years ago while walking in Turkey. We were staying overnight in a farm, and the farmer had a harvest of cobs lying out to dry. I spotted this one and got very excited – and he very kindly gave it to me (neither he nor my fellow walkers could understand why I was so happy!)

It was by studying corn cobs like these that Barbara McClintock won the Nobel Prize for discovering mobile genetic elements, in this case transposons (we are doing some work on plasmids – see previous post).

On this cob, note that most of the ears are yellow, and a few are blue. These are genetically different, and have inherited their genes in ‘normal’ Mendelian fashion. The interesting ears are the three in the centre of the image, which are yellow with coloured streaks, that are immediately below the block of five blue ears. Barbara McClintock discovered that colour streaks are caused by mobile genetic elements – pieces of DNA that have been excised and spliced – a complete different process from meiotic recombination that gives rise to Mendelian inheritance. Nobel Prize winning stuff!

Poster at the Third Biennial Workshop on Statistical Bioinformatics and Stochastic Systems Biology

Dorota Herman is attending the Third Biennial Workshop on Statistical Bioinformatics and Stochastic Systems Biology at the University of Newcastle today and tomorrow where she is presenting a poster:

Bayesian inference and evolutionary optimization of negative and cooperative autoregulation of plasmid RK2

Dorota Herman1, Christopher M Thomas2 and Dov J Stekel3

1Center for Systems Biology, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

2School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

3Integrative Systems Biology, School of Biosciences, University of Nottingham, LE12 5RD, UK

Poster Abstract

The central control operon of plasmid RK2 is an example of a natural system of negative and co-operatively autoregulation. The available data of the operon regulation by dimers of two global regulators, KorA and KorB, are insufficient for full reconstruction of the system. Therefore, we aim to explore possible dynamics of the system and to estimate unknown parameters. Additionally, we would like to contribute to the scientific discussion about the roles of negative loop in biosystems. We present possible reasons for optimization of the central control operon through comparative analyses of the wild type system with a progression of simpler systems.

Analyses of the RK2 central control operon regulation were carried out by considering the steady state of a deterministic model of the system during exponential host bacterial growth. Using the Metropolis-Hastings algorithm we have estimated protein synthesis rates and revealed insignificance of monomerization rates to the model. For evolutionary optimization analyses, we have built a stochastic multi-scale model, which includes operon regulation, plasmid replication and host cell growth and division. We have examined the architecture of the central control operon regulation and its simpler equivalents, in terms of noise, robustness, speed up in response time and burden for a host. Results have shown that possible evolutionary optimization of the central control operon might be speed up in response time and decrease in burden for a host, as indicated by a decrease in number of produced mRNA. Fluctuations and robustness do not seem to play a significant role in this case.

In summary, we have explored possible dynamics of the RK2 central control operon regulation using Bayesian framework and demonstrated possible reasons for evolution of the regulatory architecture of the naturally occuring negative and cooperative autoregulation.

Beijing Genomics Institute sequences new pathogenic E. coli strain

The Beijing Genomics Institute have sequenced the new strain using Illumina technology. Their report, which I will not reproduce, can be read here.  The sequencing confirms the combination of Shiga toxin and enteroaggerative pathogenicity factors reported by the Robert Koch Institute. The speed of the sequencing is also a remarkable testament to the power of modern sequencing technologies and associated Bioinformatics platforms.

Reflections on the bad news from KEGG

It was with great sadness that we have read about the end of funding for the KEGG database. KEGG is one of the most important Bioinformatics resources world-wide, and the first port of call for many scientists looking for information on metabolic pathways. We use KEGG in our work on bacterial luminescence, and have plans to use KEGG further in our work on pathogenic E. coli strains. It is, of course, to Kanehisa Sensei‘s great credit that he has produced and sustained this database, and we wish him all the best in his forthcoming retirement.

KEGG has become a resource of global importance. After the Tsunami and disaster at the Fukushima nuclear plant, we can understand that Japanese funding priorities have to go elsewhere. But the demise of funding for KEGG is a lesson to both academics and funders about the role of short term as opposed to perpetual funding for internationally important resources. The NCBI and EBI are both fortunate in receiving perpetual funding from the US and EU respectively, and this is the best way to ensure continuity of important bioinformatics resources. KEGG was funded by a succession of short-term grants, and so was susceptible to funding changes, and the retirement of its PI. The lesson is clear: once a resource becomes sufficiently important (and what that means may be a subject of some debate), academics, funding bodies and major institutions need to find ways of working together to ensure that that resource can be moved under the umbrella of securely funded institutions so that the resource can be maintained.