Headship Selection Committee Dept. Biomedical & Molecular Sciences
From: Donald R. Forsdyke
Date: 12th March 2012
Topic: Candidacy of David P. Siderovski
I am delighted to see
David's name on the shortlist (5th March). I have read his CV and think
I can provide a wider perspective that may be of help. I have not read
the other CVs, so this should not be taken as opposing other
candidacies. David's publications record that he has worked both in my
laboratory at Queen's and in that of Tak Mak in Toronto.
At the end of his
second undergraduate year in 1987, and armed with NSERC funding, David
applied for summer work in my laboratory. His academic record was
superlative and this was to be maintained in the years ahead. In fact,
during my two decades at Queen's, I had never before seen so impressive
an academic record. He was in a class apart from the rest. This record
was matched by his contribution to the laboratory, and he returned the
following summer at the end of his third year at Queen's.
Nearing the end of his 3-4 months in the
laboratory, he came to me one day in 1988 with the Queen's Calendar.
There was a clause stating that, if a student could make a sufficient
case, he could be excused a prescribed course, and take a course that
would be mutually agreed between student and professor. He proposed that
he not take the 4th year practical biochemistry labs, but instead spend
the entire year in my laboratory. His unusual plan was accepted by the
powers that be, and it was agreed that he would write a thesis, along
the lines of a MSc. Thesis, which would be duly examined.
David graduated in 1989 with the Prince of
Wales Prize. Given his momentum, had I had better funding I could
probably have persuaded him to stay on for graduate work. Too late, MRC
funds came in October 1989. In 1990 I was able to recruit Scott Heximer
(Ph.D 1996). You will note from the CV that David went to work with Tak
Mak and did not get his Ph.D. until 1997. Herein lies an interesting
I will begin with some personal background. In
1966 I was interviewed by Sir Peter Medawar and Avrion Mitchison at the
NIMR at Mill Hill. They saw a freshly-minted Cambridge biochemist who
might be persuaded to track down the surface receptor by which antigens
stimulate lymphocytes. I argued that, although very interesting, even
more interesting were the intracellular pathways activated when the
receptor was occupied. By differential RNA labeling, I had already
obtained "blips" showing that a host of new mRNAs were being made. These
could correspond to proteins concerned with immunological signaling, and
switching from quiescent to proliferative states. To cut a long story
short, they said no, and I came to Queen's in 1968.
The 1970s were marked
by (i) my failure to persuade the immunological establishment that
positive selection by "self" was instrumental in the generation of
lymphocyte repertoires, (ii) the sudden emergence of recombinant DNA
technology, and (iii) the identification of an antibody-like receptor on
B-lymphocytes. Then, in the late 70's there emerged a technology - "subtractive cDNA hybridization"
- which promised to help me identify my
mRNA "blips." In Toronto, Tak Mak saw similar promise for identifying
the T-lymphocyte receptor. We both needed an urgent technology upgrade.
In 1980 Mak took a sabbatical with Howard Temin at Wisconsin, and Roger
Deeley - newly arrived with tablets of recombinant wisdom from the NIH -
kindly took me into his laboratory for a 6 month mini-sabbatical.
In 1984 Tak Mak
reported the successful cDNA cloning of the T-lymphocyte receptor by a
post-doc, and in 1985 I reported the successful cDNA cloning of a group
of lymphocyte activation genes. Mak's Nature paper was accompanied by
much fanfare and a commentary proclaiming "The T-lymphocyte Antigen
Receptor - Elusive No More." My paper, presenting three cDNA clones as
examples of the group, was published in a low profile journal.
Nevertheless, I immediately began to receive requests from leading US
laboratories for recombinant samples. With money from the newly
established American Foundation for AIDS Research, I was able to keep on
my technician and fund a graduate student. But with many cDNA clones to
characterize, we needed more hands. David's arrival in the lab in 1987
Genes we identified have become "household
words." The first reported (1985) were chemokine ligand 3 (CCL3; binds
HIV coreceptor), Early Growth Response 1 (EGR1 transcription factor),
and the Fos oncogene (previously identified by others). Genes reported
later were no less spectacular. At some point, David, realizing that his
studies with Mak in Toronto were going nowhere, asked me to send him one
of the cDNA clones that, unlike our other clones, had given a smeared
blot indicating possible membership of a gene family. In Kingston, our
work on the gene led to a long paper (1994) with, as is my practice, the
junior contributor's name (David's) as first author. David was then able
to bring the full resources of the Mak and Amgen empires to further
study the gene and its product - Regulator of G Protein Signaling 2. As
you can see (publication list) - the RGS proteins have occupied much of
David's professional life.
Over the years I have
had only occasional email communications with David, but have watched
with great admiration his rise, with Scott Heximer (with whom he
sometimes co-publishes), to become a world authority on G-protein
signaling, an area of great general importance to many tissues as well
as lymphoid. Prior to going to the USA, he came at my invitation to give
a seminar. He was then deeply interested in an Assistant Professorship
at Queen's. Despite my appeals to the Head of Department that, with
David, we were in a different ballpark (i.e. a special opening should be
negotiated for him), nothing materialized. This was very disappointing.
I hope this has effectively relayed my high
estimation of David's academic and organizational skills. To round off
the tale we can note that, when reviewing the cDNA cloning of the T
lymphocyte receptor in 2007, Tak Mak posited that delays were due to "numerous technical hurdles and inaccurate concepts" that
stymie" researchers. It can now be seen that in the 1970s I had an
accurate concept, namely positive selection of lymphocyte repertoires,
but was stymied by technical hurdles and lack of funds. David's free
contribution in the 1980s partly compensated for the latter. Also in the
1980s the accuracy of my concept became apparent when Jonathan Sprent in
the USA rediscovered positive selection (not knowing of my work). All
this led to a Nobel Prize in 1996 to Zinkernagel and Doherty for key
evidence (1974) supporting positive selection (although it was not so
interpreted by them at the time).
I wish the Committee
well in its deliberations.