Paterson Institute for Cancer Research SCIENTIFIC REPORT 2005

RESEARCH SERVICES
To achieve these goals we have purchased new cameras,
light sources and more specific fluorescent filters
and mirrors to minimise light loss in transmission.
In parallel we have been fine-tuning the cell
environment on the microscope stage. The result
has been a widespread increase in live cell imaging
within the Institute and a decline in imaging fixed
samples. In short, emphasis can now be given to
the temporal dynamics of structural changes rather
than simply cataloguing snapshots of the variety of
forms within a population.
Multi-position time-lapse over the last year has
become the all more important. Many events occur
fairly infrequently, for example cell division can
occur in a 40 minute window every 24 hours, and
waiting for these events to occur in one field of
view would be prohibitively slow. Visiting multiple
points greatly enhances the return such that questions
can be asked with multi-point visiting that
would be impractical in single fields of view. We
have therefore added a high resolution XYZ stage
to our imaging platform. Several research groups
within the institute are involved in these forms of
data collection on a weekly, if not daily basis.
In the previous year we started developing systems
for controlled spot-limited photo-bleaching. These
techniques are now in routine use and have been
employed with great effect to study polymer
dynamics and the turnover of proteins on spindle
poles by Iain Hagan’s laboratory. These time-lapse
investigations are ongoing and are yielding information
about dynamics within bundles of microtubule
polymers that are simply not possible to obtain
from looking at the dynamics of an unbleached
bundle.
We are currently reviewing new fluorescent proteins
and testing particular filter/dichroic mirror combinations
to optimise transmission. We are also trying
to exploit the potential of quantum dots as a
labelling technology for both long term tissue sections
to support target validation and clinical trials
and for use in live cell imaging. It is hoped that
quantum dot technology will be in routine use in
both clinical and laboratory applications within a
year.
The increase in capabilities of the systems, in particular
the multi-point visiting and photo-bleaching
studies, are highlighting the need to keep the software
and archiving in step with the developments in
microscopes and cell culture. We are therefore
planning measures to deal with this increase in
dependence upon large scale computing platforms
and high-end software over the next year and anticipate
an increasing need for mathematical modelling
of the biological phenomena we are documenting.
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Biological Resources
http://www.paterson.man.ac.uk/facilities/bru.jsp
The Biological Resources unit continues to provide
a modern integrated service, supporting scientific
research programmes whilst ensuring that the highest
quality of health and welfare are maintained at
all times. The use of animals in medical research
remains a controversial issue and although alternative
methods such as tissue culture are used wherever
possible, there is still a need for some research
involving animals in the understanding of cancer
and the development of better treatments for
patients. All the work at the Paterson Institute that
involves the use of rodents is covered by licences
issued by the Home Office and reviewed by a local
ethical committee.
Since 2004 we have brought in several new genetically
altered strains of mice which are vital to keeping
us at the forefront of the scientific research.
Once they arrive within the BRU all the mice are
housed in individually ventilated cages (IVCs); these
cages prevent the spread of potential disease from
one cage to another, with each cage having an individual
Hepa filtered air supply and exhaust. In
addition to protecting the mice from disease these
cages also help to protect the staff from exposure
to allergens from the mice and bedding. Exposure
of staff to laboratory animal allergens (LAA) is a
current hot topic with the Health and Safety
Executive (HSE). Long term exposure to LAA can
induce asthma and skin or eye allergies in staff handling
the animals. The use of IVC caging dramatically
reduces this risk. All the cages are provided
with environmental enrichment, in the form of
nesting material and wooden chew blocks or play
tunnels. The addition of these items to the cage
provides environmental stimulation for the mice
and reduces aggression amongst males of some
strains. We undertake routine health screening
from our colonies to ensure that the mice are free
from a list of specific pathogens (SPF) and any new
strains brought into the unit are health-screened
before introduction into the facility.
Two thirds of the space in the unit has been given
over to the development and breeding of genetical-
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