From the Special Topic of
According to our Special Topics analysis of
tuberculosis (TB) research over the past decade, the
scientist whose work ranks at #7 by total cites is
Professor Stephen Gordon, with 19 papers cited a total of
3,632 times. His record in
Essential Science IndicatorsSM from
Reuters includes 40 papers, largely classified in the
field of Microbiology, cited a total of 4,325 times between
January 1, 1998 and October 31, 2008.
Professor Gordon has been an Associate Professor in the
Veterinary Sciences Centre at University College Dublin's School of
Agriculture, Food Science, & Veterinary Medicine since January 2008.
Previously, he was affiliated with the TB Research Group of the Veterinary
Laboratories Agency in Weybridge, UK.
In the interview
talks with Professor Gordon about his TB
Would you tell us a bit about your
educational background and research experiences?
I did my B.Sc. degree at University College Galway, Ireland, followed by a
Ph.D. with Peter Andrew at the University of Leicester, UK, on
mycobacterial molecular genetics. After struggling to sequence a few
kilobases of mycobacterial DNA during my Ph.D., I realized it was time to
get into genomics. Stewart Cole’s lab at the Institut Pasteur,
France, was leading the way in mycobacterial genomics, so in 1995 I went to
do a post-doc with Stewart.
"…while decoding the wealth
of information in genome sequences will take
a long time, it's going to be a fascinating
After three and a half years at the Institut Pasteur working on the human
tubercule bacillus, Mycobacterium tuberculosis, I then went to the
Veterinary Laboratories Agency in the UK to work with Glyn Hewinson on the
genomics of the animal pathogen, Mycobacterium bovis, and to
investigate how genetic differences between the human and animal pathogens
translates into their distinct host preferences. This is one of the
research angles that I am now continuing in Dublin.
What made you decide to focus on
I became interested in tuberculosis during my undergraduate degree, mainly
in the social impact that the disease had had on Irish society in the past
and the work of Dr. Noel Browne in introducing free health screening for
tuberculosis. However, I also realized that while tuberculosis was seen as
a disease of the past in many quarters, it still exacted an enormous toll
in terms of morbidity and mortality in the developing world.
From a research point of view, I was attracted to the idea of applying the
new tools of molecular biology to understand both the fundamental biology
of the causative agent, Mycobacterium tuberculosis, and how this
basic knowledge could then be translated to novel disease-control tools.
Your most-cited paper is the 1998 Nature
paper you coauthored with Stewart Cole and Roland Brosch, among others
("Deciphering the biology of Mycobacterium tuberculosis from
the complete genome sequence," 393: 537, 11 June 1998). Would
you talk a little about this paper, its findings, and its importance
to the field?
The Mycobacterium tuberculosis sequence was one of the first
genomes to be completed, and as such drew a lot of attention. In the decade
since its publication, the genome has underpinned advances across a range
of areas such as identification of diagnostic antigens, evolution of the
tubercle bacilli, discovery of virulence factors, and elucidation of novel
drug targets. There’s no doubt that the access to genome data
accelerated many advances across the field, and the citations for the paper
You were principle author on another paper with
this team, "Identification of variable regions in the genomes of
tubercle bacilli using bacterial artificial chromosome arrays." What
is it about this paper that continues to attract citations?
This paper described a range of gene-deletion events from the pathogens
that cause tuberculosis, a.k.a. the Mycobacterium tuberculosis
complex. The work gave us our first insight into how this complex of
bacteria has evolved over time, uncovered molecular markers for the
tubercle bacilli, and identified regions that may explain why the members
of the complex show such distinct host preference.
The fact that the work generated leads across these disparate areas
probably explains why the paper has been well cited. Parenthetically, the
genesis of this work was in a local bar that we frequented during my time
at Pasteur and where many good ideas were born; I often think all labs
should be within walking distance of a good bar.
A great deal of your work focuses on the
tuberculosis genome. What would you say are the most important things
that have been discovered about this genome over the
years? Do we know all there is to know about
this genome yet (or are we not even close)?
"…I also realized that while
tuberculosis was seen as a disease of the
past in many quarters, it still exacted an
enormous toll in terms of morbidity and
mortality in the developing
It’s difficult to single out one particular area where the genome has
had its greatest impact; as I’ve said earlier, the genome has
underpinned advances across many areas. From an entirely personal point of
view, it has been fascinating to see how access to genome data has altered
our understanding of the evolution of M. tuberculosis.
Prior to the availability of mycobacterial genome sequences, the
conventional wisdom was that M. tuberculosis was derived from
Mycobacterium bovis, the agent of tuberculosis in cattle. So the
idea was that when man domesticated cattle, M. bovis jumped the
species barrier to become M. tuberculosis. However, our initial
comparative genomics experiments showed that this couldn’t be the
case; M. tuberculosis was not derived from M. bovis. If
anything, the data suggested that the common ancestor of tuberculosis in
animals was more closely related to a human-adapted strain. I like these
serendipitous discoveries that change the way we think about things.
What would you like the "take-away lesson" about
your research to be?
I suppose one of the key things that anyone takes away from genome analysis
of the Mycobacterium tuberculosis complex is just how similar
these organisms are, with greater than 99.9% identity at the nucleotide
level. However, the variation in their genomes, slight as it may seem to
be, has given us a range of very successful host-adapted pathogens.
Linking these host-adaptation phenotypes back to their genetic basis is a
tall order, but the information is there, encoded in the genome and staring
us in the face; we just don’t know how to read and translate this
information into function yet. So the take-home message is that while
decoding the wealth of information in genome sequences will take a long
time, it's going to be a fascinating adventure.
Veterinary Sciences Centre
UCD School of Agriculture, Food Science, & Veterinary Medicine
College of Life Sciences
UCD Conway Institute of Biomolecular and Biomedical Research
University College Dublin, Belfield
Keywords: tuberculosis, Mycobacterium tuberculosis,
Mycobacterium bovis, complete genome sequence, mycobacterial
genomics, diagnostic antigens, evolution, virulence factors, drug
targets, host-adapted pathogens.