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Virulence profile

Virulence profile: Mark Thomas

Tell us about your early days

I was born in central London, but my parents moved to the eastern suburbs when I was still an infant. I was the eldest of four brothers and had a normal childhood. I was very keen on soccer from an early age (as was my father and his father) and all three of us supported Tottenham Hotspur FC. I was also very keen on playing cricket, and continued with the latter when I was an undergraduate and postgraduate student at university, and subsequently during my years of university employment. Music, particularly rock and blues, was an important part of my life as a teenager and as an undergraduate - I have been to many gigs and seen many of the blues greats (including Albert King, BB King, Muddy Waters, Junior Wells and Buddy Guy among the bluesers and a whole host of great rock/blues guitarists such as Jeff Beck, Jimmy Page (at a Led Zeppelin gig), Eric Clapton, Peter Green, Stevie Ray Vaughan, Johnny Winter, …the list goes on… but sadly not my all-time favorite - Jimi Hendrix).

Did you have a particular career wish as a child?

I was always very interested in natural history/biology - bringing all sorts of things home from the fields and woodlands near to my house. This had a knock on effect regarding my career aspirations while at school, which passed through phases of wanting to be an old-style “naturalist,” veterinarian, medic and then finally a research scientist in the field of biochemistry/physiology. It was for a degree in the latter that I enrolled at the University of Southampton, where I subsequently dropped the physiology and added more chemistry and microbiology. I loved my time as an undergraduate (as is the case for most people) and realized that a career in research was my destiny. I stayed on in Southampton to do a PhD in the field of microbial genetics. The career decisions I took were purely my own but they had the full support of my parents who were only too happy to have a son go to university.

What was your first position after university?

During my PhD I wrote to several PIs at universities in the US regarding the possibility of carrying out postdoctoral research on various aspects of gene regulation in bacteria (transcription activation and repression, transcription termination etc) and was offered a position in Masayasu Nomura's laboratory at the Institute for Enzyme Research at UW-Madison. Masayasu had an excellent pedigree and followed this with some exceptional work on ribosome assembly and then latterly the regulation of ribosome synthesis in bacteria, specifically the mechanism of translational feedback regulation by ribosomal proteins. This was a very novel concept when it was first discovered in his laboratory as it undermined the prevailing idea that the regulation of gene expression occurred exclusively at the level of transcription. During my tenure in Masayasu's laboratory he moved to UC-Irvine and I accompanied him to the new labs on the West Coast. It was a great experience to live in 2 very different parts of the US.

When and where did you start your own laboratory?

I joined the University of Sheffield Medical School as a PI (“Lecturer”) in 1994. The plan was to make a move from elucidating fundamental processes of gene regulation in bacteria to investigating mechanisms of bacterial pathogenicity, although I wasn't quite sure which organism I was going to tackle. Not long after starting my new post, a medical student on secondment to the PHLS/infectious diseases diagnostic laboratories in the adjacent Royal Hallamshire Hospital gave a talk to my department on an opportunistic bacterial pathogen that just been renamed as Burkholderia cepacia but was formerly known as Pseudomonas cepacia. I became very interested in this organism (which we now know to represent a group of very closely related species referred to as the B. cepacia complex) and started working on it with my first PhD student, Kate Farmer. The strains we studied are now recognized as B. cenocepacia and most of my work has focused on this organism (although my group has investigated pathogenicity mechanisms in B. pseudomallei and the related species, B. thailandensis).

About Mark Thomas. Mark Thomas is a Senior Lecturer at Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School. He obtained his first degree in Biochemistry at the University of Southampton,following which he spent a further period at the same institution investigating the genetic regulation of guanine nucleotide biosynthesis in E. coli for his PhD. This was followed by postdoctoral stints in the laboratory of Professor Masayasu Nomura at the Institute for Enzyme Research, UW-Madison, and subsequently UC-Irvine to where Prof. Nomura had relocated. Here Dr. Thomas's work was focused on understanding how regulation of ribosomal RNA and ribosomal protein synthesis was coordinated to maximise the bacterial growth rate under any given set of nutritional conditions (growth rate control). He then spent some time working in Professor Richard Flavell's group at the Institute for Plant Science Research in Cambridge (formerly The Plant Breeding Institute) where he investigated the developmental regulation of seed storage protein gene expression. His final stint as a postdoc was in the laboratory of Professor Robert Glass at the University of Nottingham where he investigated how transcription factors interacted with RNA polymerase to regulate gene expression. He joined the University of Sheffield in 1994 and shortly afterwards developed an interest in the pathogenic mechanisms of the Burkholderia. Dr. Thomas's current research interest lies in virulence mechanisms in pathogenic members of the Burkholderia. Particular areas of interest include iron acquisition mechanisms, protein toxins and their mechanism of secretion, and the response to environmental stress, particularly the role of extracytoplasmic function (ECF) sigma factors in this process

About Mark Thomas. Mark Thomas is a Senior Lecturer at Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School. He obtained his first degree in Biochemistry at the University of Southampton,following which he spent a further period at the same institution investigating the genetic regulation of guanine nucleotide biosynthesis in E. coli for his PhD. This was followed by postdoctoral stints in the laboratory of Professor Masayasu Nomura at the Institute for Enzyme Research, UW-Madison, and subsequently UC-Irvine to where Prof. Nomura had relocated. Here Dr. Thomas's work was focused on understanding how regulation of ribosomal RNA and ribosomal protein synthesis was coordinated to maximise the bacterial growth rate under any given set of nutritional conditions (growth rate control). He then spent some time working in Professor Richard Flavell's group at the Institute for Plant Science Research in Cambridge (formerly The Plant Breeding Institute) where he investigated the developmental regulation of seed storage protein gene expression. His final stint as a postdoc was in the laboratory of Professor Robert Glass at the University of Nottingham where he investigated how transcription factors interacted with RNA polymerase to regulate gene expression. He joined the University of Sheffield in 1994 and shortly afterwards developed an interest in the pathogenic mechanisms of the Burkholderia. Dr. Thomas's current research interest lies in virulence mechanisms in pathogenic members of the Burkholderia. Particular areas of interest include iron acquisition mechanisms, protein toxins and their mechanism of secretion, and the response to environmental stress, particularly the role of extracytoplasmic function (ECF) sigma factors in this process

How many people work in your laboratory?

The number of researchers is in a state of flux. Last year there was one postdoctoral research scientist and 7 PhD students, but 3 of them have since been awarded PhDs. We also have some technical support. From time to time the group is augmented by undergraduate or masters research project students.

What is your position at your institution?

Currently I am a Senior Lecturer. The post involves teaching (as the job title would suggest) and quite a bit of administrative work, in addition to leading a research group. The admin can be frustrating as I really enjoy the research and there seems to be more of it each year, but it is a part of university life and it has to be done!

What areas or topics does your laboratory currently focus on?

The entire research group is focused on mechanisms of pathogenicity in members of the genus Burkholderia. This includes iron uptake processes, stress sensing and response mediated by ECF sigma factor systems and the role of the type VI secretion system in delivering effector proteins into target cells. They really are a fascinatingly diverse group of organisms that play important environmental and (potentially) biotechnological roles as well as being the cause of some very problematic infections.

Do you have partners that are important for your research projects?

Yes. I collaborate with structural biologists and experts on tetraspanins who are all based in Sheffield.

What was your most significant scientific accomplishment?

Gosh! That's a tough one to answer. There is work I am very proud of that is not published in a very high impact factor publication while in contrast there is work published in a high impact factor scientific journal that is not of much interest to me now, although no doubt significant. There is some work I haven't yet published that is very interesting and I am very proud of it - although whether it would be deemed significant enough by my peers to be accepted by a prestigious journal is another matter altogether. If I had to choose something based on its significance, then some of the work I did in the Nomura laboratory on translational regulation would be up there, particularly demonstrating that the region of mRNA to which ribosomal proteins bound, to repress their own translation, adopted a secondary structure that mimicked the binding site for the ribosomal protein on rRNA. This observation implied that ribosomal proteins were using the same region on the protein to recognize both RNAs.

What were your “highlights” in recent research performed in your field?

It's definitely got to be the discovery of the type VI secretion system (T6SS) and the elucidation of its mechanism. The T6SS is a bacterial injection machine that delivers effector proteins into eukaryotes and other bacteria. It is therefore involved in virulence and for establishment of bacterial species in environmental niches through competition with other bacterial species. As an anti-bacterial device it may offer potential as a novel therapeutic strategy.

What do you think you would do if you were not a scientist?

That's another tough one to answer! When I was younger, I would fantasise about a variety of alternative careers - mainly ‘Boy's own’ stuff like being an explorer, a guitarist in a band (I do play, but not very well) or playing sport at a high level (in my case it would have been football (soccer) or cricket (as a spin bowler)). The reality is somewhat different. It is more likely I might have done something that involves caring for animals, i.e. a veterinary surgeon, conservation work, working in a zoo etc. Of course, that would have involved retraining.

What do you do for fun?

There's not too much time for that these days, but I do find playing the guitar (electric) at home relaxing (although learning a piece of music can be frustrating). I also like traveling to destinations that allow me to indulge my interest in natural history. At the end of 2014 I went on an overland trip from Kenya to Rwanda via Uganda to see the mountain gorillas and chimpanzees. In 2015 it was the lemurs of Madagascar, and I have arranged a trip to the Pantanal in Brazil for later this year to see jaguars, tapirs and giant anteaters (among other things). These were (and hopefully the Pantanal will be) fantastic experiences. I also like to visit India - it has everything!

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