Meet FEMS Expert: Professor Victoria Shingler

27-06-2017 Erin Frick

Professor Vicky ShinglerProfessor Victoria Shingler is a member of the European Academy of Microbiology (EAM). The EAM is a leadership group of around 130 eminent microbiology experts who came together in 2009 to amplify the impact of microbiology and microbiologists in Europe.

Prof. Victoria Shingler performed her post-doctoral research within the laboratory of Michael Bagdasarian (1985-1987), at what is now the Department of Molecular Biology, Umeå University, Sweden. She has remained at the same institution ever since, first as a group leader (1987-1989) and then as a lecturer (docent, 1990-1995). In 1995 she was awarded a ‘Särskild forskartjänst’ – a special six year researcher position sponsored by the Swedish Natural Science Foundation (NFR).

Could you tell us what you are currently researching?

“The fitness of bacteria to survive and compete within a given environment relies on their innate ability to withstand stress and adapt for optimal metabolism under prevailing conditions. Within our research we use a wide range of purpose-designed genetic and biochemical approaches to elucidate the underlying molecular mechanism by which bacteria perceive their surroundings through regulatory signals, and how they integrate multiple and sometimes conflicting signals to choreograph appropriate changes in their gene expression and ultimately their behaviour. Our primary experimental organisms are two metabolically robust root and soil dwelling Pseudomonas putida strains – KT2440 a long standing workhorse of environmental biotechnology – and CF600, which possess the unusual capacity to completely mineralise (methyl)phenol pollutants via a specialised suite of catabolic enzymes encoded by the dimethylphenol dmp-system.

Specific and global regulators converge to determine under what conditions, and in response to what compounds, the metabolically expensive production of the catabolic enzymes is undertaken. We have used the dmp-system as a molecular probe in a holistic approach to uncover different layers of regulation that can be integrated to control a single process – these include not only many factors that operate at the transcriptional and/or translational level of enzyme production, but also flagella-mediated taxis systems that allow bacteria to relocate to more optimal niches for their catabolism. In all cases, the interrelated parts of our research into these decision-making processes are designed to address fundamental questions in microbial physiology and to provide the basis for the informed design of circuits used within systems biology and environmental biotechnology.”

Current work

“One focus of our current research concerns the master regulator of (methyl)phenol catabolism –  DmpR – a member of a specialized family of mechano-transcriptional activators known as bacterial enhancer binding proteins (bEBPs). Proteins of this family utilize conformational changes produced upon hydrolysis of ATP to unlock transcription by an alternative form of the transcriptional machinery (s54-RNA polymerase). DmpR acts as a direct phenol-detector by virtue of its activation only upon binding specific aromatic compounds. At present, we are using genetic, structural, and modelling approaches to understand how a linker region of DmpR serves as a gatekeeper of its ATPase and transcriptional promoting ability.”

Challenges

“All areas of research pose their own technical and interpretational challenges – none more so than dissecting inputs from global regulatory networks. By their very nature, such regulatory factors cause cascades of regulation and pleotropic effects, which makes discerning their mode of action on a given system particularly perplexing and thought-provoking, but ultimately satisfying to solve. As one example, the nucleotide alarmone ppGpp, whose production heralds nutritional stress, has multiple regulatory inputs that result in a >1000-fold increase in transcripts of the dmp-structural genes without any discernible direct effects on the specific promoter that directs their transcription. Rather, this massive regulation results from the integration of effects on the composition of the RNA polymerase holoenzyme pools, transcriptional and translation control of DmpR levels, and DNA supercoiling transmission. Within this area of our research, we are currently analysing the biochemical properties of the post-transcriptional regulators Hfq and Crc from P. putida and P. aeruginosa, with the aim to elucidate the molecular basis for differences in their specific and global regulatory roles in hierarchical assimilation of carbon sources.”

Enter, Serendipity

“Once expressed, the enzymes of the dmp-system promote directional movement towards the substrate source through metabolism-dependent taxis. While identifying the receptor responsible for this behavioural response, we serendipitously discovered a role of an unusual bi-functional c-di-GMP signalling protein for general motility. Like ppGpp, c-di-GMP is a near ubiquitous bacterial second messenger molecule that is involved in controlling diverse physiological processes. Currently we are using genetic, biochemical and protein localization studies to track a signal transduction pathway originating from a co-transcribed surface receptor, through the c-di-GMP signalling protein to a c-di-GMP binding effector protein, and from there to the flagella motor.”

What is your research team like?

“Over the years my research group has varied in size, from one (me) to more than ten, and has been composed of an eclectic mix of people from all over the world, representing over 20 nationalities. During the last year, group members have consisted of myself, three PhD students, one post-doctoral fellow, two guest PhD students, and an undergraduate project researcher.

Physically, we are all usually located in the same large laboratory and its adjacent offices – a configuration that promotes multiple day-to-day interactions. Experiments that use specialized or large equipment (e.g. culturing, protein purification and imaging) are conducted in nearby dedicated equipment rooms located in the same building. While co-localization is the norm, group members frequently visit other labs for specific training in research techniques.

Within our research group, all co-workers are primarily responsible for their own research line, but are also actively engaged in collaborations within their area of interest. Collaborations are initiated on an ad hoc basis – either by us for approaches that use expertise we lack, or by others that request our help. For example, the PhD student driving the project on the bEBP DmpR is also heavily engaged in two collaborative projects concerning other bEBPs that control type VI secretion and phenylalanine catabolism, while the post-doctoral researcher is simultaneously developing his own line of research and collaborative network.”

Could you tell us a little about yourself?

“Personally, I have always loved the experimental over writing aspects of science. While one obviously rejoices over the successes of co-workers, there is nothing quite like being the first see an image or plot emerge and realize exactly what it means. Given time constraints, my hands-on work is usually restricted to the more ‘microbial’ aspects of our research, which are experimentally longer-term but require only a short daily period at the bench. Nevertheless, regular strolls through the lab with an experienced eye can be amazingly productive – rescuing an ‘odd’ looking colony from being discarded as a ‘contaminant’ has on many occasions been the first key step in understanding what is going on or identifying a precious mutant.”

You can find out more about the microbiology experts within the EAM here.

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