Research Interests:
Research combines two main interests: viruses
and proteins. We study the complex bacteriophage T4, which has been of enduring
interests to molecular biologists since this field was born some 45 years ago.
There are four experimental lines we are currently pursuing:
1) The
development of a pulse-chase protocol that will reveal the entire assembly
pathway in vivo. This is an ambitious project that promises to resolve some of
the most difficult unanswered problems in virus morphogenesis. It will provide
us with the precise time of addition of each protein and also give us the first
quantitative measure of each protein's intracellular pool size.
2) We are
also studying head expansion, an important step in head morphogenesis. As the
DNA enters the empty head shell, the shell expands 15% in dimension and 50% in
volume. We are trying to identify the initiator of expansion and the mechanism
by which it is transmitted from one end of the capsid to the other.
3)
The possible chaperone role of gp57A in the folding of the short tail fibre, a
trimer of gp12. By now the fact that one protein can help another to fold or
oligomerize is well established. These so-called chaperones have been isolated
from every living organism from bacteria to plants and animals. Here we have
such a pair, and we will explore the folding and aggregation intermediates of
gp12 in various gp57A backgrounds to observe when and where the latter exerts
its effects.
4) The structure of the T4 baseplate. We have carried out
cross-linking experiments which have permitted the mapping of most of the 15
proteins that make up the baseplate at the bottom of the T4 tall. Its central
hub, however, remains an enigma, for it failed to give many contacts and has
long been the most difficult subassembly to isolate and work with. We have
cloned two of the genes which two groups have shown to be in, or not to be In,
the central hub. We plan to now Investigate whether they are In the finished
structure and what role they play In baseplate and hub
morphogenesis.
Special Responsibilities/Interests
/Expertise:
Coordinator of Biology- Chemistry Program
Recent
Publications:
Ferguson, P.F., and D.H. Coombs. 1997. Identification of
bacteriophage T4 virion proteins by transverse pore-gradient SDS polyacrylamide
gel electrophoresis and dual amino acid labelling. Electrophoresis 18:
xx-xx.
Chen, Mathews, Wheeler, Maley, Maley and Coombs. 1995. An Immunoblot Assay
reveals that Bacteriophage T4 Thymidylate Synthetase and Dihydrofolate Reductase
are not virion proteins. J. Virology 69:2119-25.
e-mail to: dhc@unb.ca
Maintained by: casey@unb.ca
Last Update: 29 March 1998
This
document: http://www.unb.ca/web/Biology/Faculty/Coombs.html