Marsden Fund Newsletter
No 11 April 2000
Contents
- Why antisense helps stop brain damage
- New Zild as she is spoke
- New microscope spots single atoms
- News from Marsden Cottage
- Why a rare native dolphin is in decline
- Marsden at a glance
- The case of the vanishing nitrogen
- Why life may have crawled out of nature's spa pool
- How cosmic rays help us understand the Earth's surface
Why antisense helps stop brain damage
Marsden researchers have made a pioneering discovery that could dramatically
reduce the spread of brain damage, help regenerate the spinal cord and increase
wound healing.
Working with so-called antisense technology, the Auckland University team
has been tweaking the communications between living cells by altering the links
between them. Antisense mechanisms work at the genetic level to interrupt the
process by which proteins are produced.
The remarkable results came to light by accident after a researcher blocked
cell-to-cell communication by using antisense to limit the production of the
"gap junction" protein, connexin43, in brain tissue. The process has
already been patented.
Associate Professor Colin Green in the Department of Anatomy with Radiology
at The University of Auckland said his group was the first to use the antisense
approach to separate out the role of direct cell to cell communication in regulating
the genes involved in making limbs and growing tissue. Gap junction channels
allowed cells to communicate with each other.
"This communication is essential during development, as well as in adult
tissues where, for example, it reorganises damaged tissue or co-ordinates contractions
of the heart muscle cells," he said. "To study the role of these channel
proteins, our team had worked with chick embryos."
Professor Green said Lee Yong Law, a graduate student in the laboratory, was
carrying out this Marsden-funded work for his PhD. The project had included
studies on the fusion of embryonic tissues and the regulation of blood and limb
development.
The dramatic results came to light during work on neural protection and wound
healing, he said. "When honours student Vicki Milham joined our group,
she concentrated her work on the brain. We know that the brain damage spread
which occurs over the 24 to 48 hours after injury was through toxins moving
via gap junction channels.
"These spreading waves cause the injury to spread. The research group
came up with a way to regulate the gap junction proteins in damaged brain tissue.
The remarkable result was that lesions in antisense-treated cerebral cortex
were up to 50 percent smaller than untreated lesions.
"We passed on this information to a colleague, Dr David Becker at University
College London, who applied the technique to spinal cord injuries. Here, we
found we could not only block lesion spread, but also stop inflammation."
Professor Green said there were four main steps to spinal cord regeneration.
"First, there is the need to contain the injury and stop spread; second,
the need to reduce the inflammatory response which leads to connective tissue
'scar' formation in the damaged region blocking neuronal regeneration; third
is the need to get neurons regrowing; and last, we have the need to guide their
connections.
"In one treatment, we have made significant progress in understanding
and ameliorating two of these four steps."
Professor Green explained how Dr Jun Sheng Lin, a research fellow with his
group, decided to take the study further. "It was necessary to wound the
skin over the skull when studying brain lesions, and connexins play a major
role in skin growth control and patterning after wounding. Dr Lin therefore
applied the antisense to skin lesions and noted an increased rate of healing.
This is because the epithelial cells are released to divide more rapidly. As
the transient antisense effects wear off, they can migrate in a co-ordinated
fashion over the wound.
"In addition, the same anti-inflammatory effect seen in the spinal cord
comes into play, and scar formation should be reduced. Again, our colleagues
in London had access to an excellent, well-established wound healing model system
and were able to corroborate our results," Professor Green added.
A patent was taken out last year in relation to these discoveries, he said.
"While there is a long way to go before we see clinical use, the advantages
of a natural product which can be targeted to a specific gene product at a specific
time point are enormous. For instance, the product could be used to minimise
damage to surrounding tissue following brain surgery, or to aid healing after
a skin graft.
"This is a classic example of fundamental research leading, through a
series of fortuitous circumstances, to large potential benefit."
For further information, contact Associate Professor Colin Green, Department
of Anatomy with Radiology, Phone: (09) 373 7599 ext. 6135, Fax:
(09) 373 7484, Email: c.green@auckland.ac.nz
Address: The University of Auckland, Private Bag 92 019, Auckland
Associate Professor Colin Green and Dr Jun Sheng Lin.
New Zild as she is spoke
Pitch tracks for the utterance "Why are we in a limo?", read by a
female speaker (left) and a male speaker (right) of New Zealand English. It
is clear that the female speaker both uses a larger range (compare the scales)
and has more dramatic movements in her pitch contour. The rise in pitch at the
end of a sentence, particularly characteristic of female speech, is well illustrated.
The way New Zealand men and women use pitch differently when speaking is
the subject of a Marsden project by researchers from the school of Linguistics
and Applied Language Studies at Victoria University.
Nicola Daly and Paul Warren are exploring gender differences in intonation
patterns, part of the first comprehensive study of intonation in New Zealand
English.
"We are looking at various parameters that relate to the prevalent stereotypes
of female speech as 'shrill', 'overemotional' and 'swoopy', labels that suggest
that women may use a more extensive and varied range of pitch than men,"
Dr Warren said.
In their study of the way a sample of young (1619) New Zealanders speak,
the researchers looked at broad distinctions between the speech of women and
men. Included here were such issues as the width of the pitch range used by
each individual and the dynamic range of their pitch (how often and how rapidly
their pitch varies), along with more detailed measures of the point at which
speakers change the direction of their pitch contour (tune-text alignment).
"We have found that female speakers do have a significantly wider and
more varied pitch than men. The question arises, why are men and women using
intonation differently?" asks Dr Warren.
"It is possible that that the purpose of this gender difference is to
differentiate
male and female speech. However, this can usually be done with reference to
the pitch levels used: male speech is generally at a lower pitch than female
speech.
"We suggest instead that the intonation patterns highlighted in our study
are fully compatible with New Zealand studies of gender differences in conversational
speech. These show that women interrupt less, use more minimal feedback (such
as 'mmm' and 'yes'), make more use of tag questions (such as 'isn't it?' and
'can't he?') to encourage interaction from their conversational partner and
give and accept more compliments."
Daly and Warren conclude that the negative stereotypes that label women's
speech "shrill" or "overemotional" are misguided. They suggest
that the broader and more dynamic pitch pattern used by New Zealand women works
to maximise attention and interest from their conversational partner, and helps
ensure clearer communication.
For further information, contact Dr Paul Warren, School of Linguistics and
Applied Language Research, Victoria University of Wellington, Phone:
(04) 463 5631, Fax: (04) 463 5604, Email: Paul.Warren@vuw.ac.nz,
Address: P O Box 600, Wellington
New microscope spots single atoms
An idea hatched at The University of Auckland by a group of Marsden-funded
physicists led to the creation of a groundbreaking microscope that can trap
and observe a single atom at a time.
The so-called "atom cavity microscope" was built at the Californian
Institute of Technology (Caltech). In an experiment reported in the February
25 issue of Science, caesium atoms were trapped one at a time in microscopic
orbits inside an optical cavity and their motion was monitored in real time.
The optical cavity is the basis of the microscope and consists of a pair of
highly reflective mirrors facing one another across a space of just 10 microns.
"Weak laser light is shone into the cavity and the atom is trapped with
forces exerted by the tiny amount of light bouncing back and forward between
the mirrors; so tiny that on average just a single photon (the elementary 'particle'
of light) is inside the cavity at any one time," explained Auckland physicist
Dr Scott Parkins, who first proposed the technique.
"The interaction between the atom and the light can be used to 'watch'
the atom."
Working with Andrew Doherty, also from the Quantum Optics group at Auckland
University's Physics Department, Dr Parkins developed models for the motion
of the atoms in the experiment as part of a Marsden research programme led by
the late Prof. Dan Walls.
"This work realises a new and unique measurement capability for tracking
single atoms and the idea and theory for the experiment comes from our work
here in Auckland," he explained.
In order to detect the atoms, the experimental group at Caltech, led by Prof.
Jeff Kimble and postgraduate student Christina Hood (also a New Zealander),
measured the light coming out through one of the cavity mirrors. Only certain
colours (frequencies) of light can pass through the cavity but exactly which
colours depends on whether there is an atom in the cavity and on where that
atom is.
The amount of light coming out through the second mirror changes dramatically
as the atom moves around, thus providing a sensitive measure of the atom's position.
The group used this information to create "movies"
of the atomic motion.
The movies show atoms orbiting around the centre axis of the cavity in a plane
parallel to the mirrors. Each orbit takes about 150 microseconds and the radius
of the orbit is usually less than 20 microns.
The group was able to determine the atomic position to within about 2 microns
in a time of about 10 microseconds. This combination of accuracy and speed made
it possible to track the orbital motion of the atoms.
"The ability to 'watch' such tiny objects may in the future allow researchers
to gather new kinds of information about chemically and biologically important
processes by monitoring the individual molecules involved in chemical and biochemical
reactions," Dr Parkins explained.
"The experiment also constitutes an important step forward in controlling
and observing a system in which the physics is governed by the laws of quantum
mechanics, the theory of the microscopic world developed early last century
by,
amongst others, Einstein, Heisenberg and Schroedinger.
"This new capability will be important for the eventual creation of quantum
technologies such as quantum computers and quantum communication, which offer
potentially huge advances over present-day systems."
Dr Parkins said that quantum computers make use of some of the strange and
unique properties of quantum mechanics to facilitate a kind of massive parallelism,
which can in principle be used to solve certain problems that are currently
intractable using conventional computers.
"A particularly important example is finding the prime factors of very
large numbers (with, say, 250 or more digits), which forms the basis of present
encryption schemes for the secure transfer of confidential information."
For further information, contact Scott Parkins, Physics Department, The University
of Auckland, Phone: 649373 7599 ext. 6282, Fax: 649373
7445, Email: s.parkins@auckland.ac.nz,
Address: Private Bag 92 019, Auckland
News from Marsden Cottage
by Dr Valda McCann, Manager, Marsden Fund
This year we received 756 preliminary Marsden Fund applications, a handful
less than last year (773). Following an initial selection by the eight panels,
the Marsden Committee will shortly invite about 16% of applicants to submit
full proposals. As in previous years, the standard of the preliminary applications
has been extremely high. Sadly, this means that many worthwhile proposals will
be turned down, and many strong applicants disappointed. However, much excellent
research will be funded, research that otherwise might not have proceeded. The
Mathematical and Information Sciences applications have increased in number
this year. Last year there was some concern about the downward trend in these
applications so it is heartening to see the increase.
Coming on top of the NERF funding round, the last three months have been a
busy time for applicants. The Marsden Fund and the Foundation for Research,
Science and Technology are currently discussing ways of ensuring that proposals
are directed to the appropriate fund, to avoid duplication of effort.
In this issue of Marsden Update, we feature articles on seven of the
300 current or recently completed projects. The work of Colin Green's group
at Auckland, using antisense technology, is an outstanding example of serendipity.
The contribution of Scott Parkins and Andrew Doherty to an atom cavity microscope
is yet another example of New Zealanders at the leading edge of quantum optics.
The value of such fundamental research is being recognised by Government.
In a speech on 17 March, the Minister of Research, Science and Technology, Hon.
Pete Hodgson, set out the Government's three priorities in science and technology:
encouraging more private sector research; increasing public funding for basic
research; and improving the direction of strategic research. Speaking specifically
about the Marsden Fund, Mr Hodgson said that curiosity-driven, non-strategic
research was a vital part of the science portfolio, and the Government is committed
to increasing it.
Table 1 Data on preliminary applications, by panel, for 1999 and 2000.
The numbers include proposals sent to more than one panel so the total number
of assessments by panel (834, the same as last year) is more than the number
of separate applications.
|
Number of preliminary proposals |
| Panel |
1999 |
2000 |
| Biochemical and Biomedical Sciences |
115 |
126 |
| Cellular, Molecular and Physiological Biology |
171 |
158 |
| Ecology, Evolution and Behaviour |
175 |
189 |
| Earth Sciences and Astronomy |
79 |
83 |
| Humanities |
37 |
32 |
| Mathematical and Information Sciences |
46 |
61 |
| Physical Sciences and Engineering |
119 |
103 |
| Social Sciences |
92 |
82 |
| Total |
834 |
834 |
|
|
Why a rare native dolphin is in decline
The North Island Hector's dolphin, one of two subspecies of this native
marine mammal, sticks close to home and avoids deep water. These rare creatures
are also prone to getting tangled up and drowning in gillnets, a factor blamed
for their serious decline over recent years.
Researchers Dr Scott Baker and PhD student Franz Pichler from the School of
Biological Sciences at Auckland University are attempting to reconstruct the
history of this decline. Their work is part of a wider Marsden project investigating
the genetic diversity of whales, dolphins and sealions.
As part of their research, they have studied DNA extracted from bone and teeth
of museum specimens dating back to 1870. By comparing the genetic diversity
of this material with present-day dolphins, they have learned that the North
Island Hector's dolphin has faced a severe decline and is now probably inbred.
They have also found that the localised populations around the South Island's
east coast have experienced a recent period of decline.
"Hector's dolphin provides a unique example by which to understand the
changes in genetic diversity due to behavioural isolation and population declines,"
Franz Pichler explained.
"By examining variation at genetic markers which are not influenced by
natural selection, like the maternally inherited mitochrondrial DNA and bi-parentally
inherited microsatellites, we can assess the extent of breeding between groups.
"Fundamental questions within conservation biology include firstly, the
degree to which the small size of a breeding population affects future viability,
and, secondly, whether inbreeding gets rid of damaging mutations or causes a
drastic loss of advantageous properties," he continued.
"Our current investigation into loss of diversity in a group of genes
associated with the immune system, is directed towards this second question.
A loss of diversity for these genes would indicate a reduced resistance to disease
and a loss of potential for adaptation to future environmental changes."
For further information, contact C. Scott Baker at the School of Biological
Sciences, The University of Auckland, Phone: (09) 373 7599 ext. 4588,
Email: cs.baker@auckland,ac.nz, Address: Private Bag 92 019, Auckland
Hector's dolphins, Kaikoura.Photo: I. Cepaniek
Marsden at a glance
The Marsden Fund supports excellent research, in a wide range of topics covering
the sciences, social sciences, humanities and engineering.
Each year, Government provides funding for projects that will foster research
of the highest calibre. This is work not subject to government priorities but
will nonetheless enhance New Zealand's ability to participate in, and benefit
from, research of an international standard. Set up in 1994, the Marsden Fund
is a contestable fund administered by the Royal Society of New Zealand.
A Marsden Fund Committee of 10 eminent researchers, chaired by Professor Diana
Hill, is appointed by the Minister of Research, Science and Technology to make
recommendations for funding. Selection criteria focus on the merit of the proposal,
the potential of the researchers to contribute to the advancement of knowledge,
and the enhancement of research skills in New Zealand, especially those of emerging
researchers.
Eight panels have been established to help the Marsden Fund Committee assess
proposals. These are:
- Biochemical and Biomedical Sciences
- Humanities
- Cellular, Molecular and Physiological Biology
- Mathematical and Information Sciences
- Earth Sciences and Astronomy
- Physical Sciences and Engineering
- Ecology, Evolution and Behaviour
- Social Sciences
For more information and application forms, contact the Marsden Fund c/o the
Royal Society of New Zealand, 9 Turnbull St, Thorndon, P O Box 598, Wellington,
New Zealand, Phone: (644) 4728345Fax: (644) 4731409Email:
marsden@ rsnz.govt.nz
The case of the vanishing nitrogen
Soil scientists have long been perplexed at the mysterious fate of the gases
released when nitrate fertilisers and organic wastes are added to pasture.
In particular, the whereabouts of the nitrous oxide gas emitted by so-called
denitrification has assumed greater relevance in recent years because it is
both a greenhouse gas and ozone-depleting substance.
Now a Marsden-funded project involving a team of scientists led by Dr Robert
Sherlock of the Centre for Soil and Environmental Quality at Lincoln University,
has the missing gases in its sights. The team, which includes Dr Timothy Clough
and Professor Keith Cameron, is using the stable isotope of nitrogen (15N)
as a tracer to follow the progress of nitrogen in pasture soils. Only rarely
is this tracer fully accounted for.
"Researchers have assumed that isotope not recovered equals the amount
of nitrogen lost by denitrification, a process in which nitrate is converted
to nitrogen and nitrous oxide," Dr Sherlock explained.
"In principle, direct measurements of the 15N-labelled nitrogen
and nitrous oxide emissions from the soil surface should account for all of
the non-recovered tracer
at the end of the experiment when soil, leachate and plants are sampled.
"However, when experiments are conducted in which surface gas emissions
of 15N-labelled gases are measured, there is often an unaccounted
for 'loss' of nitrogen isotope from the soil plant system, greater than 10 percent."
The Lincoln team has two theories for the lost nitrogen: (i) that entrapped
denitrification gases are displaced down into the earth during rainfall or irrigation;
and (ii) that disturbing the soil during sampling releases pockets of gas. These
gases are therefore lost from the study system and remain unaccounted for.
"To investigate these ideas, we initially studied the movement of nitrous
oxide," Dr Sherlock explained. "We placed soil cores in a purpose
built gas-tight glovebox. Irrigation and continuous gas sampling occurred via
inlet/outlet ports. We applied a nitrate solution to the soil core to stimulate
denitrification and later irrigated it.
"As the applied water infiltrated down through the soil core, nitrous
oxide was displaced out the bottom of the soil core, increasing its concentration
in the glovebox atmosphere. When the soil core was broken open the nitrous oxide
entrapped inside the soil pore space was likewise, 'released' into the glovebox
atmosphere."
Dr Sherlock said the results had confirmed the team's theories. "These
two mechanisms provide possible explanations for the contradictory results obtained
when comparing direct measurements of denitrification (surface fluxes) with
the 'unaccounted for 15N' in mass balance studies.
"While we performed this particular experiment with unlabelled nitrate,
further experiments are underway in which 15N labelled nitrogen and
nitrous oxide are being measured.
"In a 15N recovery experiment the contribution of these two
mechanisms in accounting for the 'unaccounted for 15N' will depend
on the concentration of denitrification products present, the frequency and
volume of irrigation/rainfall and the duration of the experiment."
For further information, contact Dr Robert Sherlock at the Lincoln Soil Quality
Research Centre, Lincoln University, Phone: (03) 3252811, Fax:
(03) 3253607, Email: sherlock@Lincoln.ac.nz, Address: P
O Box 84, Lincoln University, Canterbury
Changes in glovebox nitrous oxide concentration over time. (a) Nitrate solution
applied. (b) Water applied to soil core surface and nitrous oxide concentrations
increase due to displacement by the water. (c) Glovebox opened and nitrous oxide
concentration returned to ambient. (d) Soil core rapidly extruded and physically
broken open causing a large increase in concentration from nitrous oxide that
had yet to diffuse or was entrapped in the soil core.
Why life may have crawled out of nature's spa pool
Did life as we know it have its beginnings in hot springs-like environments?
A Marsden project led by Professor Hugh Morgan of Waikato University is testing
the fascinating idea that the biochemical reactions that power all forms of
life began at high temperatures.
The project is investigating the most readily available energy source to drive
enzyme reactions as life evolved. Professor Morgan believes the source was the
high energy phosphate bonds found in pyrophosphate (PPi), rather than the high
energy phosphate bonds found in adenosine triphosphate (ATP), the more common
source in present-day metabolism.
"This idea developed because of the widely held belief that the metabolic
reactions that preceded cellular life arose in hot spring-like environments
and the fact that PPi is formed continuously in geothermal systems.
"Based on this hypothesis, present-day organisms that most closely resemble
the ancient forms of life (thermophilic bacteria, i.e. those that grow at high
temperatures, and a more primitive form of bacteria called Archaea) might be
expected to retain traces of the ancient metabolism," he said.
Professor Morgan said the idea was being tested with the aid of an enzyme
called phosphofructokinase (PFK). This is a key enzyme in the breaking down
of glucose in the cell, part of the process of producing cellular energy. The
enzyme usually uses ATP as its energy source but in some species it uses PPi
as its source.
"We have shown that Dictyoglomus, one of the organisms thought
to have evolved the least from the primeval life form, does indeed use PPi rather
than ATP," he said.
"Similarly, the enzyme from thermophilic species of Spirochaeta
also uses PPi though in this instance the same type of enzyme is found in all
the spirochaetes investigated that grow at average temperatures. We have obtained
the DNA sequence for the PFK gene from several thermophiles, and will soon have
sequence information for all known variants of the PFK gene which will allow
some assessment of their evolutionary position."
Another strand of the research is looking at thermophilic Archaea. These are
widely thought to represent the least evolved of all current life forms.
"A German group had already established that one genus of thermophilic
Archaea possessed a PPi-dependent PFK enzyme. Unexpectedly we have found a totally
novel type of PFK. We (and independently a Dutch group) have purified a PFK
that depends on a third type of phosphate energy source, called adenosine diphosphate
(ADP), in two species of thermophilic Archaea.
"Moreover we have also substantiated preliminary reports that the Archaea
possess ATP-dependent PFK enzymes. Thus, the primitive Archaea is unique in
possessing three types of PFK enzyme while all other forms of life are only
known to possess one or two.
"When we obtain DNA sequence information on all three types of Archaeal
PFK genes, sequence analysis will allow us to trace the evolution of the enzymes(s)
and determine the original ancient form. This may well have profound implications
for theories on the origin of life itself.
"We are also making progress on the crystallisation of the PFK variants
(in collaboration with Dr Moore from Massey University) which might provide
insights into the evolution of the active site of the enzyme," he concluded.
For further information, contact Professor Hugh Morgan, The University of Waikato,
Phone: (07) 838 4705, Fax: (07) 838 4324, Email: h.morgan@waikato.ac.nz,
Address: Private Bag 3105, Hamilton
Orakei Korako, near Rotorua.Photo: Ruth Munro
How cosmic rays help us understand the Earth's surface
Kiwi scientists are harnessing homegrown technology to improve a technique
that helps track the changing landscape due to erosion, glaciation and the movement
of tectonic plates.
The method relies on measuring the trace amounts of beryllium and other isotopes
produced in the surface of rocks by cosmic rays hitting the Earth. The amount
of isotope in a rock can be used to infer how long the rock has been exposed,
in the geologically important range from 10 thousand to half a million years
ago.
Beryllium isotopes, for example, are generated in minerals like quartz in
rock surfaces. This occurs through the interaction of cosmic rays, mainly neutrons,
with atoms of oxygen and silicon.
As part of a Marsden project to measure the amount of beryllium produced in
unit time (i.e., production rate), sealed containers of water have been placed
at locations in Antarctica, Australia and New Zealand, with data collected every
6 to 12 months.
Project leader, Dr Ian Graham, from the Insititute of Geological and Nuclear
Sciences, said the size and weight (115kg) of the water containers, and their
remote locations, had led to difficulties in deploying them. At Mt Erebus and
Mt Taranaki, for example, helicopters were needed and the weather had to be
perfect.
Dr Graham said the research was being approached in two ways. The first involved
measuring beryllium isotopes produced in the water containers exposed to cosmic
rays at locations of varying altitude and geomagnetic latitude. The second approach
was measuring cosmic ray (neutron) flux at the same, and other selected, locations.
"We are measuring neutrons using a home-built, portable neutron measuring
device, the first of its kind in the world. Two instruments have been constructed,
the first acting as a base station to monitor short and long-term variations
in the flux," he said.
"The second instrument has been used to obtain neutron flux data in Antarctica
(Scott Base Mt Erebus), eastern Australia (Cape York Newcastle)
and New Zealand (Dunedin to Kaitaia; also Mt Hutt, Mt Ruapehu and Mt Taranaki)."
Dr Graham said that initial results from Antarctica, Dunedin and Taranaki
were encouraging, with calculated annual production rates close to theoretical
predictions.
"Together with the results from the water targets, the neutron flux data
is being modelled and compared with theoretical results and direct measurements
of cosmogenic nuclide production rates from the Northern Hemisphere," he
said.
"They will then be used directly to improve the surface exposure dating
technique in New Zealand and internationally."
For further information, contact Dr Ian Graham, Insitute of Geological and
Nuclear Sciences, Lower Hutt,Phone: (04) 5704 677, Fax: (04) 5704
657, Email: i.graham@gns.cri.nz,
Address: P O Box 31312, Lower Hutt
Dr Ian Graham (centre) and Neil Whitehead (left) placing water targets on Fanthams
Peak, Mt Taranaki.
Marsden Update is published quarterly by the Marsden Fund and is available
free on request.
Editor: Redmer Yska,
Email:
red.yska@clear.net.nz
