Professor Frank Gibson -
Half a Century of Research
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Introduction
In September 1937 a vacancy occurred for a junior laboratory technician
in the Bacteriology Department in the University of Melbourne.
I had just turned 14 and I left the Collingwood Technical College
and my work for the Senior Technical Certificate to take the position.
The next 2 years provided an excellent grounding in the basics
of bacteriological techniques and I was then shifted to one of
the research laboratories where I assisted in experiments on the
antibacterial activity of acridines.
In 1940 I was encouraged by the head of the department, Professor
H.A. Woodruff, and my supervisor, Dr. (later Professor) S.D. Rubbo,
to apply for the technical officers position in the embryonic
Bacteriology Department within the Pathology Department in the
University of Queensland.
One attraction of the position was That the University would
pay my fees to take a part-time B.Sc., 2 years of which could
be taken over 4 years at night classes.The only other member of
staff in bacteriology was Dr. D.F. Gray a Senior lecturer in the
Veterinary faculty.
As we were required to provide courses for medical, dental and
science students I found that I was not only preparing material
for the practical classes but also acting as a demonstrator. One
of the medical students at the time was Malcolm Whyte who I was
encounter many years later when he was Head of the Department
of Clinical Science in the John Curtin School (JCSMR).
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Before starting the work for my degree I had to overcome the hurdle
of matriculation. The University of Queensland was very lenient and
after taking into account the work I had done as part of the Evening
Chemistry Diploma at the Melbourne Technical College admitted me after
I passed Leaving Chemistry and Physics. This took a year and, except
for a year which I spent in the army, I settled down to a routine of
4 nights a week at classes and the weekends surfing and climbing mountains
in south-eastern Queensland. This life style involved an intensive period
of "swotting" at the end of the academic year and would not have been
possible under the current regimes of continuous assessment.
At the beginning of 1947 I returned to the Bacteriology Department in
Melbourne to finish my degree, majoring in Biochemistry and Microbiology,
employed as a Research Assistant, my University fees being paid by a
post-war serviceman's grant.
First independent research
While I had been involved as a research assistant in a variety of projects
ranging from the antibacterial action of acridines to the efficacy of
various pertussis vaccines, I was now employed as a Senior Demonstrator
and had the freedom to spend some of my time on a project of my own
choosing. I had developed an interest in the mode of action of antibacterials
and decided to look at the action of various acridines on oxidase enzymes
on the assumption that they might be asserting their action as metabolic
analogues of riboflavin. This work resulted in a paper the main importance
of which was to allow me to get a postgraduate scholarship.
Postgraduate study
I was fortunate to be awarded an ANU postgraduate scholarship in the
early days of the JCSMSR when the scholarships were taken in the UK.
I was married to Margaret Burvill in 1949 and we both went to Oxford
and worked for our Doctorates of Philosophy (D. Phil.) My immediate
supervisor was D.D. Woods who had discovered the mode of action of the
sulfonamides and Sir Howard Florey authorised the cost for attendance
at conferences etc and arranged for me to become a member of Lincoln
College.
My main project was to find the source of the terminal methyl group
of the amino acid, methionine. The principal techniques used were the
nutrition of normal and mutant bacterial cells, and the use of washed
suspensions of whole cells. The project was successful although the
work was not published for some years because "DD" became ill. Before
we sailed for home I was offered the choice of 2 positions and decided
to return to the University of Melbourne to a Senior Lecturership
Teaching and research
The next few years were spent teaching courses in general bacteriology
and microbial biochemistry and building up a viable research group.
Grants were obtained from the NHMRC, the Robertson Committee (the precursor
of the Australian Research Grants Committee) and, eventually, from the
National Institutes of Health in the USA.
My interest still lay in the mode of action of antibacterials and we
developed a method of using mutants of Aerobacter aerogenes to
test the effects of antibiotics on the biosynthesis of aromatic amino
acids. The intermediates in the biosynthetic pathways were the study
of active research in various laboratories and our interest changed
to the outstanding problem at the time, namely the "branchpoint" compound(s)
in the pathway. Several compounds were known to comprise the "common
pathway" of aromatic biosynthesis which eventually branched at one or
more points to give the amino acids tyrosine, phenylalanine and tryptophan.
We obtained some evidence of tHe existence of a labile compound which
could act as a precursor of the three aromatic amino acids and this
was isolated and its structure determined.
About this time the group was fortunate enough to attract a group of
gifted graduate students including C.H. Doy, A.J. Pittard, G.B. Cox,
I.G. Young and R.G.H. Cotton. Margaret Gibson was an active post doctoral
member of the group but unfortunately became ill and was unable to further
her research career. A valuable collaborator was found in Professor
L.M. Jackman, an NMR spectroscopist, who provided the final evidence
for the structure.
The new compound was found to be the precursor of aromatic compounds
other than the amino acids and was named chorismic
acid  .
Studies on the metabolism of chorismic acid uncovered new pathways to
aromatic vitamins and iron-transporting compounds opening up the study
of new genes and enzymes. These were exciting times in the lab in the
mid 60s as there was always something new to turn to if one line of
work was not going well.
Move to JCSMR
In 1966 I was offered the Chair in Biochemistry in the JCSMR and took
it up in the beginning of 1967.To my delight almost all the group in
Melbourne decided to transfer to new positions in Canberra and the work
was not severely interrupted.
Work continued exploiting the opportunities offered by studying the
metabolism of chorismic acid. For example chorismic acid was shown to
be a readily converted to 4-hydroxybenzoic acid which, in turn, was
converted, by a series of enzymes to the vitamins ubiquinone and menaquinone
(vitamin K). By this time we had changed the organism we used to Escherichia
coli because of the advantages of being able to carry out genetic studies.
The ubiquinone pathway alone resulted in the genetic mapping of eight
undescribed genes and six new compounds and opened up the possibility
of studying the enzymic reactions concerned. Aromatic iron-binding compounds
were found and their biosynthetic pathways studied.
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The diagram indicates the various pathways studied and, as indicated,
the functions of the quinones and iron-binding compounds were
studied using the various mutants isolated in the course of the
work.
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The study of ubiquinone and its role in aerobic oxidations led us
into the field of bioenergetics and in 1970 a new class of mutant was
discovered in which mutants with normal ubiquinone levels, but impaired
oxidative capacity were found to be deficient in the ability to form
the important protein complex responsible for the synthesis of ATP (ATP
synthase). This important finding was to determine the course of my
work, in collaboration with G.B. Cox) for a quarter of a century. We
characterised the gene-polypeptide relationships for seven out of the
eight genes coding for the proteins of the ATP synthase protein complex
and mutants were used to investigate its structure, assembly and function
Since my retirement in 1988 I have been mainly concerned collaborating
with members of the research groups within the JCSMR and elsewhere in
computer-based examination of the structure of various membrane-bound
and soluble proteins, includingmolecular modelling. In the 63 years
since I first went to work in a laboratory I have been fortunate in
always having something I found exciting to do with an outstanding group
of colleagues.
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A more detailed description of the of the work mentioned above can be
found in "Chorismic acid and beyond. Gibson, F. in A History of Biochemistry
- Personal Recollections Part IV; Comprehensive Biochemistry, (Slater,
E, Semenza, G and Jaenicke, R. Eds.) (1995) 38, 259-30.
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