The following members of the CGR were successful
in the latest round of Marsden Fund grants:
CONGRATULATIONS to our researchers who have been
successful in the 1999 Funding Round for Marsden Fund grants. All
grants but one are over 3 years.
Professor Warren Tate and Dr Liz Poole; Biochemistry;
The mammalian translational termination signal: a sequence element
involved in gene regulation?
The solution of the genetic code for protein synthesis provided
an explanation of how information in DNA is interpreted to provide
specific proteins. A critical feature was the definition of very
specific 'start' and 'stop' signals for the synthesis process. Subsequently,
there have been indications that the 'stop' signal is much more
complex. We will define the signal for humans and other mammals,
and investigate hints that a larger 'stop' signal is important for
regulating amounts of specific mammalian proteins.
Professor Anthony Braithwaite and Dr Merilyn
Hibma; Pathology and Microbilogy; $570,000
A co-factor requirement for p53 mediated apoptosis.
This proposal aims to test the hypothesis that the p53 tumour suppressor
needs to bind a co-factor in order to be competent to cause cell
death. This hypothesis derives from a number of observations with
adenoviruses which suggest that p53 dependent death induced by the
virus requires binding of a viral protein (Elb55k) to p53. The experiments
described herein aim to explore this (new) paradigm of p53 mediated
cell death with adenoviruses and to extend it to other p53 binding
proteins (E6 from human papilloma viruses and the cellular mdm 2
protein) that function similarly to Elb55k.
Professor Christine Winterbourn; Pathology,
Oxidant targets in cell signalling.
External signals regulate many functions of cells, including growth
and death, by initiating a cascade of molecular responses. Reactive
oxygen species such as hydrogen peroxide can initiate some of these
responses. They may also transmit the effects of other molecules
that bind to cell surface receptors. it is not known how these oxidants
act. We aim to determine whether hydrogen peroxide selectively oxidises
specific thiol proteins to change their properties in a way that
promulgates the signalling cascade. Our objective is to identify
such proteins and probe the molecular mechanism of this fundamental
Dr Brian Monk; Oral Sciences & Orthodontics;
$300,000 (over 2 years)
Breaking the mould through structural resolution of a prototypic
Extensive work on the genetic manipulation, function, isolation
and crystallisation of the yeast plasma membrane proton pump positions
us to tackle the 3-dimensional structure of this prototypic P-type
ATPase. High-resolution X-ray crystallographic models of this enzyme
will illuminate how the membrane ATPase functions. The analysis
of fungal ATPase-inhibitor complexes will pioneer the application
of structure-directed design for surface-active inhibitors of individual
P-type ATPases. This, in turn, will provide new mechanistic classes
of medicines and agrichemicals, including fungicides, and circumvent
the intracellular detoxification and multidrug resistance mechanisms
that are curtailing the "age of antimicrobials".
Dr Richard McKnight; Biochemistry; $360,000
Isolation of novel flowering time genes using transposon launching
Little is known about how the time at which a plant flowers is controlled.
In recent years, substantial progress has been made in our understanding
of flowering through the characterisation of plant genes that when
mutated cause a change in the time the plant flowers. In this project
we employ a new method (using plant transposable elements) to isolate
and characterise two novel flowering-time genes. We will determine
the function of these genes using genetic and molecular biological
techniques. Understanding how the genes work to control when a plant
flowers will provide a significant advance in our understanding
of flowering and plant development.
Dr Geoff Tompkins and Associate Professor J
Tagg; Oral Sciences & Orthodontics and Microbiology; $384,000
Bacteriocin-facilitated gene acquisition.
Dr Michael Roy and Professor P Mladenov; Zoology;
Using unique New Zealand fauna to examine the evolution of animal
Starfish are excellent models for studying body plan evolution amongst
animals. We will document the role of body patterning genes amongst
a diversity of starfish families and construct a robust starfish
phylogeny by combining a battery of datasets using novel computational
methods. This project aims to elucidate: 1) if changes in the expression
of body patterning genes has provided the mechanism for the evolution
of new body plans and life history strategies in starfish and 2)
the order and tempo of evolutionary events relating to changes in
body plan and whether the development of basic body plans remained
labile late in starfish evolution.
Associate Professor Clive Ronson; Microbiology;
Evolution of a Microbial Genome.
With our discovery of the symbiosis island of Mesorhizobium loti,
we demonstrated a novel mechanism through which bacteria grow their
genomes and adapt to environmental niches. The symbiosis island
is neither phage nor plasmid but represents a novel class of acquired
genetic element that integrates into the chromosome at a tRNA gene.
In this proposal, we examine the hypothesis that such "fitness islands"
are widespread and play a more significant role in bacterial evolution
than currently recognised. We will determine the extent of acquired
DNA adjacent to a tRNA locus in members of a population of soil
bacteria, andcharacterise the acquired genetic elements. The outcome
will be fundamental new insight into mechanisms of bacterial adaptation
and evolution, and the nature of the genetic elements involved.
Dr Hamish Spencer; Zoology; $415,000
Genetic models of the evolution of genomic imprinting.
Otago has won $8,224,000 in this round (Auckland
$5,175,000) and this represents 28.8% of the total pool of $28,574,000.
Well done and congratulations again to all!