As an undergraduate Brian read Botany
at the Queen’s College, Oxford, graduating in 1962. He was
awarded a Christopher Welch Scholarship to support his DPhil research
on genetic recombination in bacteria, under the supervision of E A
Bevan.
During his postgraduate training he attended a course in
Naples on the genetics and physiology of bacterial viruses that had a
lasting influence on his scientific interests and his experimental
design.
After a brief period at Queen Mary
College, London, Brian joined the laboratory of Paul Howard-Flanders
at Yale University School of Medicine, as a postdoctoral research
associate. Howard-Flanders was a British-born geneticist
interested in the mechanisms of replication, recombination and repair
of DNA molecules.
Together with Dean Rupp and others, they published
several important papers on the replication and recombination of
bacterial DNA that had been damaged by UV irradiation.
In 1969, Brian was recruited by Bob
Pritchard to join the new Department of Genetics at the University of
Leicester. There he continued to work on processes
related to DNA recombination, with increasing emphasis on the role of
plasmid-borne genes in the transfer of DNA between bacterial cells as
well as the nature of the bridge between donor and recipient bacteria
that allows the movement of genetic material between the two cells.
Using bacteriophage to destroy donor bacteria, the
recipients being resistant, he was able to show that labelled membrane
proteins from the donor were transferred to the membranes of the
recipient, providing strong evidence for membrane fusion during
mating.
As early as 1975 he produced evidence
for a genetic interaction between certain plasmid genes and host genes
encoding components of the cellular DNA replication machinery.
Developments of this observation in his laboratory led to the
discovery of a plasmid gene encoding DNA primase, an enzyme crucially
involved in the initiation of DNA replication. Using the
same approach to destroying the donor Wilkins and his colleagues
established that the plasmid-specified primase protein was transferred
from the donor to the recipient cell during the bacterial ‘mating’
event, and that this could occur in the absence of DNA transfer.
These important observations on plasmid-mediated protein export now
make sense in light of the genetic relatedness of the cognate
transport proteins and components of secretion systems associated with
several clinically important bacterial pathogens, including
Legionella pneumophila, the cause ofLegionnaires’ Disease.
Brian’s interest in plasmid biology
and horizontal gene-transfer fuelled a continuing study of the genetic
interactions between the plasmid and the recipient cell, in which the
newly transferred DNA encounters a potentially antagonistic
environment. He pioneered the studies that have shown that
the first few plasmid genes transferred are immediately expressed in
the recipient cell to produce proteins that help to protect and
establish the incoming DNA in the hostile environment.
Plasmid-encoded proteins block host-specific degradation
(‘restriction’) of the incoming DNA, inhibit the potentially suicidal
‘SOS’ response and augment a potentially limiting host protein that is
necessary for DNA replication. The relevant plasmid genes
are expressed in a transient burst by a mechanism that unusually were
hypothesised to involve utilisation of the single-stranded transferred
DNA as the template for RNA polymerase.
Brian’s most recent studies, in
collaboration with biochemical colleagues, involved exploration of
this hypothesis that the single-stranded DNA folds into a unique
secondary structure that creates a temporary template for RNA
polymerase. Replication of the transferred strand in the
recipient would necessarily destroy this special secondary structure
and self-limit the burst of gene-expression.
Brian was also a pioneer in thinking
about how to use genome sequence information to tell you more about a
plasmid than how many open reading frames it encodes, what their
products are related to and what regulates their expression. His
study of the RP4 genome sequence demonstrated that the genomic
signature of this plasmid, a marked deficiency in targets for certain
groups of restriction enzymes, must be the result of selection during
transfer between strains of its preferred host.
Brian’s approach to laboratory
investigation was reflective and careful. He relished the
planning process, designing the controlled experiment that would test
the current hypothesis.
Early in his career a referee assessed him as
‘interested, original, ingenious and effective’: that perceptive
description remained true throughout his career. He worked
with a small team, often a technician and a PhD student, sometimes a
single postdoctoral associate, but was able to make an internationally
recognised scientific contribution over two decades.
Brian received frequent invitations
to speak or chair sessions at international meetings and to write
reviews for leading journals. As a speaker he was thoughtful and
thought-provoking. He was meticulous in his preparation and
exceptional in the clarity with which he developed his argument and
presented the logic of the work he was describing. He was
also a very effective university teacher, caring deeply about the
welfare of his students and the quality of their educational
experience. This interest in students was also
reflected in his interactions with younger colleagues at Leicester and
more broadly in the scientific community. He was great fun to be
with and was one of those colleagues that it was a real pleasure to
meet up with in a railway station or an airport on your way to a
workshop or conference.
Brian had a wide circle of friends
and colleagues and it is a clear mark of the esteem with which we all
regarded him that as the news of his death last April spread there was
a feeling that we should set up a memorial in his name. Brian
identified the Plasmid Biology community as his scientific home and in
recognition of the encouragement that he gave to young scientists we
have decided that a fund should be set up to award on five occasions a
Brian Wilkins Memorial Prize at the International Plasmid Biology
Conference. The Prize will be for a young scientist working on
plasmids, other mobile genetic elements or horizontal gene transfer
who has carried out excellent science and can communicate it well.
More details are shown in the Rules of the Prize attached to the end
of this announcement.
We realise that Brian was just one of
many who have made the study of Plasmids such an exciting field of
research. We hope that by awarding this prize we will not only
keep alive the memory of what Brian did, but also encourage the
community to remember how important it is to understand our scientific
roots and those that laid the foundations of our modern science.
(This description of Brian's work
is based on text written by Bill Brammar, for Leicester University,
and for an obituary that appeared in "The Independent" on 12th June
2003)
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