Mini-Project - University of Glasgow

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2 Οκτ 2013 (πριν από 3 χρόνια και 10 μήνες)

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BBSRC Mini
-
Projects 2012


Institute of Neuroscience and Psychology


Dr Lars Muckli

(
Lars.Muckli@glasgow.ac.uk
)

Title:

Spatial tuning
of cortical feedback

Mini
-
Project
:

We will measure the spatial precision of cortical feedback
projections. The fMRI
brain reading experiments will investigate the spatial tuning of contextual feedback
information. Two natural images (i.e. image of a street scene and a forest) will be
presented to six subjects. The stimuli
-
set will be presented in ¾

of the visual field
and the lower right visual field quadrant is occluded by a plain white rectangle.
Retinotopic mapping will be used to map out the cortical region that is processing
the occluded part of the image. Information at this cortical position
will process the
constant feed
-
forward information (the white occluder) and the cortical feedback
that contains some contextual information of the scene (Smith & Muckli 2010,
PNAS). Critically, the stimuli will be presented with different spatial shifts (0
deg,
2deg, 8deg). V1
-
V3 activation patterns will be extracted and used for information
decoding (Smith and Muckli 2010, PNAS). A multi
-
voxel pattern classifier will be
trained to distinguish the different natural visual scenes with 0
-
deg shift and will be
tested to cross
-
classify images with the different spatial shifts (2deg 8deg). As the
cross
-
classifier is trained on cortical feedback the performance of the cross
-
classifier
can tell us about the precision of cortical feedback.

Area:

Ageing


Prof
Phillipe Schyns

(
Phillipe.Schyns@glasgow.ac.uk
)

Dr
Guillaume

Rousselet

(
Guillaume.Rousselet@glasgow.ac.uk
)

Title:

Understanding age
-
related
changes in the processing of emotion information

Mini
-
Project
:

Recent studies suggest that older adults have difficulty ignoring task
-
irrelevant
visual information. This is an important hypothesis in aging research, because it
suggests that some cognitive

problems experienced by old adults have a common
origin in a deficit in filtering out distracting visual stimuli. However, the ignoring
deficit has been suggested based on poorly quantified group data only, without
consideration for individual differences
. Therefore, it remains unknown how strong
these age effects are, and what proportion of older subjects are affected. The goal
of this mini project will be to validate a new EEG technique to quantify when, and by
how much, cortical face sensitivity is modu
lated by task requirements. Once
validated in young subjects, this technique will be applied to a group of older
subjects


a second step that would be an excellent side project for a PhD student.
This project will improve on our previous attempts at quant
ifying the extent to
which the brain can ignore information when task demands are reduced:
http://www.frontiersin.org/perception_science/10.3389/fpsyg.2011.0013
7/abstract



This mini project will provide excellent training in Bioimaging and Bioinformatics. In
particular, the student will learn to design EEG experiments, test subjects,
administer questionnaires, visual tests, apply EEG electrodes and analyse resul
ts
using robust statistics.

Area:

Ageing


Institute of Molecular, Cell and Systems Biology


Prof Michael Blatt

(
Michael.Blatt@glasgow.ac.uk
)

Title:

Modelling guard cells for improved plant water use
efficiency

Mini
-
Project
:

Interaction in plants of a subset of Kv
-
like channels with plasma membrane
-
associated SNAREs leads to profound alterations in channel gating. These
interactions are thought to couple traffic with transport, coordinating these
proc
esses during cell expansion. Recent evidence suggests a voltage
-
dependence to
this interaction. The student will generate one or more mutations in the voltage
sensor of the KAT1 channel to affect the voltage
-
dependence of its mobility in the
membrane, and
will examine its functional effect on gating and on interaction with
the SNARE SYP121 by heterologous expression and voltage clamp analysis. Training
is relevant to FOOD SECURITY and to OTHER WORLD
-
CLASS SCIENCE, and will
include SYSTEMS BIOLOGY cutting
-
ed
ge methods in molecular and cell biology
(electrophysiology), as well as niche training in PLANT PHYSIOLOGY.


Area:

Food Security


Dr Nia Bryant

(
Nia.Bryant@glasgow.ac.uk
)

Prof Gwyn Gould

(
Gwyn.Gould@glasgow.ac.uk
)

Title:

Role of tyrosine phosphorylation of membrane trafficking proteins in insulin action.

BBSRC Mini
-
Projects 2012

Mini
-
Project
:

Regulation of SNARE complex assembly is central to one of the key defining f
eatures
of eukaryotic cells, their intracellular compartmentalisation into discrete membrane
bound organelles. This project will use an in vitro approach to test the hypothesis
that phosphorylation plays a key role in this process, focussing on the tyrosi
ne
phosphorylation of Munc18c and the cognate t
-
SNARE Syntaxin 4. Phosphor
-
mimetic mutants of these proteins will be expressed and purified from bacteria, and
used in a range of in vitro assays. IN particular, we will assay the impact of
phosphor
-
mimetic m
utants on the structure of the proteins (using circular
dichroism), rates of SNARE complex formation and the Kd for interaction of
Munc18c and Syntaxin 4. These assays are already in place within the group, and
will equip the student with a good grounding
in protein expression/purification, and
exposure to biophysical approaches that underpin subsequent in vivo analyses.

Area:

Other World
-
Class Biosciences


Prof Shireen Davies

(
Shireen.Davies@glasgow.ac.uk
)

Prof Julian Dow

(
Julian.Dow@glasgow.ac.uk
)

Title:

Insecticide
-
responsive nuclear receptor/transcription factors in xenobiotic
resistance

Mini
-
Project
:

Transcriptional targets
of the insecticide
-
responsive nuclear receptor dHNF4
regulated by different insecticide classes will be assessed via Affymetrix Drosophila
Genome 2.0 microarrays of tubule cDNA samples. Although RNA
-
seq is an
alternative, Affymetrix arrays are reliable and

cost
-
effective. We also have extensive
experience of tissue
-
specific Affymetrix microarrays, and of associated data analysis.
We will:


1. define the tubule transcriptome in response to 2 different classes of insecticides
compared to untreated controls.

2. define transcriptional targets of dHNF4 by carrying out experiments as Aim 1 but
in knock
-
down lines of dHNF4 (tubule
-
targeted RNAi), available from the VDRC stock
collection (http://stockcenter.vdrc.at/control/main). We will compare the tubule
transc
riptome in response to 2 different classes of insecticide (as Aim 1) with
untreated knockdown controls, but with additional parallel experiments performed
on control parental lines.


The results from proposed experiments will provide definitive data on xen
obiotic
-
associated genes in a key xenobiotic
-
handling tissue, and will identify the genes
regulated by dHNF4. Comparison of these datasets and further analysis will define
epithelial ‘markers’ for xenobiotic handling; and identify novel genes in
detoxifica
tion responses.

This project, in the Food Security Research Priority Area provides training in key
Skills Priorities: transcriptomics, bioinformatics, systems biology.

Area:

Food Security


Prof Gwyn Gould

(
Gwyn.Gould@glasgow.ac.uk
)

Dr Nia Bryant

(
Nia.Bryant@glasgow.ac.uk
)

Title:

Role of tyrosine phosphorylation of membrane trafficking proteins in insulin action.

Mini
-
Project
:

It is vital that eukaryotic
cells are able to respond to extracellular signals by altering
trafficking pathway


this is essential for many physiological processes. Membrane
trafficking events are regulated by the formation of specific SNARE complexes, a
process which in turn is reg
ulated by members of the SM family of proteins. This
project will test the hypothesis that the phosphorylation of Munc18c in response to
insulin directly regulates the formation of Syntxin4 containing complexes which in
turn regulates the delivery of Glut
4 to the plasma membrane. This will be achieved
by expressing phosphor
-
resistant and phosphor mimetic versions of Munc18c in
3T3
-
L1 adipocytes in culture. This mini
-
project will generate the required expression
constructs (allowing the student to gain expe
rtise in molecular approaches) and
then selection and analysis of stable cell clones. In tandem, the student will
establish conditions for knockdown of endogenous Munc18c.

Area:

Other World
-
Class Biosciences


Dr Iain Johnstone

(
Iain.Johnstone@Glasgow.ac.uk
)

Dr Christopher McInerny (
Christopher.McInerny@Glasgow.ac.uk
)

T
itle

Regulation of the CDC
-
25.1 phosphatase during development in
Caenorhabditis
elegans
: an interdisciplinary approach

Mini
Project:

Project
-

The hallmark of many human diseases is the loss of control of cell division,
which in extreme cases leads to the for
mation of tumours and malignancy. This PhD
BBSRC Mini
-
Projects 2012

studentships will study causal mechanisms than lead to oncogenesis in the model
eukaryotic organism, the nematode worm
Caenorhabditis elegans.
We have already
shown, in a series of publications, that mutation in t
he cell cycle control
phosphatase CDC
-
25.1 leads to tumourgenesis. The PhD student will extend this
important observation, by analysing the role of the CDC
-
14 phosphatase in this
process.


Using an interdisciplinary approach the student will use a fission
yeast
Schizosaccharomyces pombe
model system that we have developed to complete
biochemical studies of modification of CDC
-
25.1 activity by phosophorylation; such
studies are impossible in worms because of limited cellular material. Once
important amino ac
id residues have been identified in fission yeast that are
modified by CDC
-
14, we will mutate the same residues in worms, to search for
function and importance in tumourgenesis in this organism. Thus the student will
exploit two organisms and use a wide ra
nge of techniques to study a fundamental
and important medical problem.

Area:

Ageing



Dr John Christie

(
John.Christie@Glasgow.ac.uk
)


Title:

Phototropin phosphorylation of ABA Signalling Components

Mini
Project:

Drought is the most important limiting factor for crop production. Stomatal function
is key in this regard, as the opening and closing of these pores regulates both CO
2

uptake for photosynthesis and water loss via transpiration. Blue light is a key factor
that drives stomatal opening. This is achieved primarily through the action of a small
family of photoreceptor kinases known as the phototropins (phot1 and phot2).
Conv
ersely, the phytohormone abscisic acid (ABA) promotes stomatal closure under
drought stress to prevent water loss. Elucidation of the mechanisms underlying the
crosstalk between blue light and ABA signalling are of physiological importance, as
plants in th
eir natural habitat are simultaneously exposed to light, as well as
drought stress. Investigating the crosstalk between these pathways forms the basis
of this project. We have found that the protein phosphatase HAB1 (Homology to
ABI1), a core component of
ABA signalling is a direct substrate target for phot1
kinase activity. This project will use plant physiology and biochemical approaches to
investigate how HAB1 phosphorylation by phototropin blue light receptors
functions as a molecular link that integrat
es light and phytohormone signalling in
plants.

Area:

Other World Class Bioscience



Institute of Infection, Immunity & Inflammation


Prof Sarah Cleaveland
(
Sarah.Cleaveland@glasgow.ac.uk
)

Prof
Massimo Palmarini

(
Massimo.Palmarini@glasgow.ac.uk
)

Title:

Bluetongue virus infection in domestic dogs in Tanzania

Mini
-
Project
:

Bluetongue is a disease of widespread concern to the livestock industry in the UK
and Europe. Although the disease is generally considered a disease of ungulates, it
is known that dogs can be infected with the bluetongue virus (BTV), can mount an
antibody

response, and in some cases show clinical signs of disease. Infection is
thought to be possible through the oral ingestion of infected meat as well as vector
transmission. In East Africa, BTV is thought to occur widely as a highly endemic
infection and
previous studies in the Serengeti ecosystem provide evidence of high
levels of virus circulation in a range of wild ungulate and carnivore species, including
buffalo, gazelles, lions, jackals, and hyenas. This project aims to investigate BTV in
domestic d
ogs in the Serengeti, to investigate the potential role of dogs as sentinel
hosts to identify high
-
risk areas of infection, and to investigate the possible role of
domestic dogs in onward transmission of BTV. The project will involve serological
analyses
of archived serum samples from domestic dogs collected over a 10
-
year
study period in the Serengeti ecosystem, comparing infection patterns in areas of
the ecosystem that differ according to climatic and ecological characteristics. In
addition, molecular a
nalyses will be carried out on EDTA blood samples collected
from domestic dogs as part of on
-
going rabies vaccination campaigns in the
Serengeti to investigate the prevalence of viraemic dogs, and potential onward
transmission of BTV in a highly
-
endemic ar
ea.

Area:

Food Security



BBSRC Mini
-
Projects 2012


Dr Gillian Douce

(
Gillian.Douce@glasgow.ac.uk
)


Title:

You are what you eat: Investigating the Interlinked Cycle of Relationships between
Host Gut Microbiome, Immune System
and Systemic Infection

Mini
-
Project
:

The impact of gut flora (the microbiome) on health and disease is emerging as a key
area of biomedical research. Underpinning this project is increasing evidence that
the microbiome shapes the host immune system and
its response to infection. This
project will test the hypothesis that the microbiome has a major impact on the
immune response to parasitic infections, such as the medically and economically
important infections caused by trypanosomes. This research may le
ad to the
development of novel therapeutic intervention strategies. Indeed, the potential for
eventual treatment of humans and large animals is considerable. For example, it
may be possible to modify the microbiome of humans or cattle with probiotics to
in
crease their tolerance of trypanosome infections. This would have a major
medical and economic impact. This mini
-
project will focus on using standard
bacteriological culture techniques together with the latest sequencing approaches
to characterise the alte
rations in the components of the gut microbiome associated
with trypanosome infection. This method will provide essential baseline data for the
broader associated PhD project
.

Area:

Food Security


Prof Paul Garside

(
Paul.Garside@glasgow.ac.uk
)

Title:

You are what you eat: Investigating the Interlinked Cycle of Relationships between
Host Gut Microbiome, Immune System and Systemic Infection

Mini
-
Project:

The impact of
gut flora (the microbiome) on health and disease is emerging as a key
area of biomedical research. Underpinning this PhD project is increasing evidence
that the microbiome shapes the host immune system and its response to infection.
This project will test
the hypothesis that the microbiome has a major impact on the
immune response to parasitic infections, such as the medically and economically
important infections caused by trypanosomes. This research may lead to the
development of novel therapeutic interve
ntion strategies. Indeed, the potential for
eventual treatment of humans and large animals is considerable. For example, it
may be possible to modify the microbiome of humans or cattle with probiotics to
increase their tolerance of trypanosome infections.
This would have a major
medical and economic impact, as trypanosomiasis is not only a life
-
threatening
infection in humans but is also currently estimated to cost $1 billion/year by limiting
the suitable area for cattle rearing in sub
-
Saharan Africa. This
studentship will
provide an excellent inter
-
disciplinary training opportunity and unique skill set in
this burgeoning area of biological research and

the outcomes of this study will have
major implications for global health of human and domestic animal pop
ulations.



Area:

Food Security


Dr Annette MacLeod

(
Annette.MacLeod@glasgow.ac.uk
)

Title:

You are what you eat: Investigating the Interlinked Cycle of Relationships between
Host Gut Microbiome,
Immune System and Systemic Infection

Mini
-
Project:

The impact of gut flora (the microbiome) on health and disease is emerging as a key
area of biomedical research. Underpinning this project is increasing evidence that
the microbiome shapes the host immune

system and its response to infection. This
project will test the hypothesis that the microbiome has a major impact on the
immune response to parasitic infections, such as the medically and economically
important infections caused by trypanosomes. This res
earch may lead to the
development of novel therapeutic intervention strategies. Indeed, the potential for
eventual treatment of humans and large animals is considerable. For example, it
may be possible to modify the microbiome of humans or cattle with prob
iotics to
increase their tolerance of trypanosome infections. This would have a major
medical and economic impact. This mini
-
project will focus on developing a novel
strategy based on the ‘safe
-
sequencing system’ to accurately quantify the bacteria
in any
given sample. This approach will overcome the inherent bias of PCR
amplification, which is the current standard. This method will be enhance the
analysis of the associated PhD project but will also be broadly applicable to the
wider microbiome research com
munity
.

Area:

Food Security


Dr Gillian Douce

(
Gillian.Douce@glasgow.ac.uk
)

Title:

Role and composition of microbiota in relapse of C. difficile infection

Mini
-
Evidence from recent sequence analysis of the human Microbiome suggests that no
BBSRC Mini
-
Projects 2012

Project
:

single species or strain is essential for maintenance of a healthy gut. It is more likely
that specific combinations of bacteria with co
-
ordinated but linked metabolic
pathway
s contribute to homeostasis and suppression of pathogen growth and
inflammation. In healthy individuals and in animal models, C. difficile disease can
only be initiated by the modification of the flora as a consequence of antibiotic
treatment. However, t
he mechanism by which the microbiota suppresses
germination and outgrowth of the C. difficile are unclear. The aim of this project
will be to optimise the conditions for isolation of aerobic and anaerobic bacteria
from faeces from animals resistant or sus
ceptible to C. difficile infection (pre and
post antibiotically treated). Isolates will be identified by 16S sequencing and the
role these bacteria play in the control of germination and outgrowth of C. difficile
growth will be considered. The impact of
specific isolates will be considered
individually or in combination with 16S analysis allowing further metagenomic
analysis and allow the synthetic creation of mixtures of isolates with metabolically
complimentary inhibitory pathways. This project will req
uire an understanding of in
vivo biology, comparative genomics and systems biology.

Area:

Ageing


Dr Richard McCulloch

(
Richard.McCulloch@glasgow.ac.uk
)

Prof Jeremy Mottram
(
Jeremy.Mottram@glasgow.ac.uk
)

Title:

Identification of the network of protein kinases that control DNA replication and
repair in Trypanosoma brucei

Mini
-
Project
:

DNA repair is a central process in the
transmission of all genomes, contributing to
immune evasion in many pathogens and acting to ensure completion of DNA
replication. Repair is regulated to occur at specific cell cycle stages in a process
called the DNA damage response. Key enzymes in this re
sponse are PI
-
3 protein
kinases (PKs) termed ATM and ATR, which signal the presence of damage by
recognising, respectively, double
-
stranded DNA breaks and single
-
stranded DNA. To
date, little work has examined the DNA damage response in Trypanosoma brucei,

the African trypanosome that evades immunity through recombination
-
mediated
antigenic variation of a Variant Surface Glycoprotein (VSG) coat. Indeed,
unconventional aspects of cell division, the cell cycle, replication and repair have
been detailed in kin
etoplastid parasites, suggesting that the DNA damage response
may differ from the host. Using a recently developed RNAi library that targets the
complete repertoire of 183 PKs in T. brucei, preliminary RNAi of ATM and ATR
suggests that loss of the latter m
ay be lethal in mammal
-
infective T. brucei, though
the reasons for this are unclear. This project will validate the provisional RNAi
findings for ATM and ATR, and will examine the basis for the putative lethality
following ATR loss. This will be assessed b
y examining cell cycle progression, by
FACS and DAPI staining, and by examining DNA integrity and repair/replication
timing, using EdU incorporation. In addition, the roles of the PKs in repair will be
assessed by measuring sensitivity to induced damage an
d by examining repair factor
localisation by immunofluorescence microscopy. Finally, roles in antigenic variation
will be assayed by examining expression of VSGs by qRT
-
PCR and western analyses.

Mini
-
Project
:

Autophagy is a widely conserved intracellular
mechanism for the degradation of
long lived proteins and organelles; it is involved in many fundamental aspects of
cellular homeostasis and development. It is a complex multi
-
protein pathway
characterised by the formation of autophagosomes around cargo des
tined for the
lysosome. The ubiquitin
-
like protein, ATG8, is a key component of the
autophagosome membrane and is an established molecular marker for autophagy
in many different biological systems.To investigate the role of autophagy in growth
and developm
ent of Trypanosoma brucei we have generated reporter cell lines
expressing YFP
-
ATG8 in bloodstream form parasites. Characterisation of the T.
brucei ATG8 identified autophagosome
-
like structures that could be detected by
fluorescence microscopy. Detailed a
nalysis confirmed autophagy occurred in both
lifecycle stages and was upregulated in response to stress. To analyse the
autophagy pathway in more detail, we have created YFP
-
ATG8 expressing RNAi
compatible cell lines. Down
-
regulation of specific autophagy
pathway genes (e.g.
ATG5) disrupted the formation of autophagosomes and generated autophagy
defective parasites for in vivo loss of function analysis. RNAi depletion of TOR1
(established negative regulator of autophagy) induced autophagy, thereby
validatin
g the use of this approach for wider interrogation of potential regulators of
T. brucei autophagy pathway. This project will investigate the role of protein kinases
in controlling the autophagic pathway in bloodstream form parasite in vitro
BBSRC Mini
-
Projects 2012

(culture) and i
n vivo (animal model).

Area:

Other World
-
Class Biosciences, Food Security


Dr Markus Meissner
(
Markus.Meissner@glasgow.ac.uk
)

Title:

Organellar biogenesis in apicomplexan parasites

Mini
-
Project
:

Apicomplexan parasites are single celled eukaryotes that actively invade and
replicate within a host cell. This phylum consists of more then 5000 species,
including important human and veterinary pathogens that have a huge, global effect
on human and anima
l health. While
Plasmodium
spp. (the causative agent of
malaria) is the most notorious member of this phylum, other apicomplexans are
among the most relevant food
-
borne pathogens of global socioeconomic relevance.
For example
Eimeria
spp. are the most important protozoan pathogens of poultry,
causing a damage of ~ £1500 million worldwide per annum. Other important
foodborne pathogens include
Cryptosporidium, Neospora caninum, Theileria
or
Toxoplasma
.

These parasites evolved unique orga
nelles and mechanisms in order to actively
invade and replicate within the host cell, such as specialised and unique secretory
organelles (micronemes, rhoptries and dense granules) or sophisiticated machinery
that enables the parasite to move by gliding mo
tility. Our key focus is the functional
characterisation of factors that are involved in the biogenesis, maintenance and
regulation of these unique organelles. While the specialised secretory organelles
contain key determinants for invasion (see above), th
e IMC contains the glideosome
that provides the driving force to actively enter the host. Interestingly, these unique
organelles are linked to the secretory system of the parasite, indicating that it has
been substantially reorganised in apicomplexans to a
dapt to a parasitic lifestyle. In
fact we recently demonstrated novel mechanisms involved in organellar biogenesis,
protein transport and regulated secretion.

We combine forward and reverse genetic screens to identify conserved and novel
factors that are i
nvolved in the biogenesis, maintenance and regulation of these
organelles.

Area:

Food Security


Dr Pablo Murcia
(
Pablo.Murcia@glasgow.ac.uk
)

Title:

Deciphering the virome of rodents using metagenomics

Mini
-
Project
:

This rotation project would be conducted as part of a larger, 4
-
year project, to
investigate the virome of distinct target species in Africa that are likely to play a role
in viral emergence in both wildlife and livestock. The collaborative
group includes
scientists from the University of Glasgow (Cleaveland, Murcia, Lembo) together with
teams from the The Genome Analysis Centre (Norwich), and scientists from
Tanzania (Sokoine University of Agriculture, Central Veterinary Laboratory and
Tanz
ania Wildlife Research Institute) bringing together expertise in field
epidemiology, virology, evolutionary biology and bioinformatics. This project aims
to improve our knowledge on the underpinning mechanisms of viral emergence by
integrating concepts fro
m Virology, Bioinformatics, Evolutionary Genetics, and
Infectious Diseases’ Epidemiology. Although there is some flexibility regarding the
specific objectives, the project will all have a strong metagenomics approach. The
specific aim of this rotation proj
ect is to set up the protocols to prepare clinical
samples obtained from wildlife animals. In turn, prepared samples will be
sequenced using next generation technologies. Protocols will include molecular
biology techniques such as DNA and RNA extraction, v
iral enrichment, sequence
-
independent PCR and determination of quality and quantity of nucleic acids
obtained.

Area:

Food Security


Prof Tony Page

(
Tony.Page@glasgow.ac.uk
)

Prof Neil Bulleid

(
Neil.Bulleid@glasgow.ac.uk
)

Dr Iain Johnstone

(
Iain.Johnstone@glasgow.ac.uk
)

Title:

Shedding light on ER oxidative stress

Mini
-
Project
:

The endoplasmic reticulum (ER) is the subcellular organelle where proteins are
folded and modified prior to their secretion. A major event in this process is the
formation of disulphide bonds, an event that is highly sensitive to the redox
environment. Num
erous enzymes, oxidases and peroxidases are predicted to be
involved in the homeostasis of this redox balance to allow disulphide formation and
to prevent oxidative stress. In this mini project a Caenorhabditis elegans redox
sensitive GFP strain will be us
ed to examine a subset of ER proteins via RNAi and
determine if they are involved in redox balance in this model organism. This project
will use a bioinformatic approach to identify suitable ER candidates, these will then
BBSRC Mini
-
Projects 2012

be examined via bioimaging followi
ng RNA interference and the student will
therefore gain experience in a wide range of computer, laboratory and imaging
-

based techniques.

Area:

Ageing


Dr Daniel Walker

(
Daniel.Walker@glasgow.ac.uk
)

Tit
le:

Creation of disease resistant transgenic plants expressing species specific protein
antibiotics.

Mini
-
Project
:

In the fight for resources, bacteria produce a wide variety of antimicrobial agents to
kill competing organisms. In addition to the broad
spectrum antibiotics used in
clinical practice, some bacteria produce very narrow spectrum protein antibiotics,
known as bacteriocins, which are active only against bacteria closely related to the
producing organism. We have identified a lectin
-
like bacter
iocin from Pseudomonas
syringae that is active against other strains of this species and so could be used in
biocontrol strategies against this important plant pathogen. Little is known about
how this type of bacteriocin is able to specifically target stra
ins of Pseudomonas
syringae and the aim of this project is to determine its mechanism of action. This
will be achieved using a range of techniques including site directed mutagenesis,
protein purification, structural biology and cytotoxicity assays.

Area:

Food Security


Institute of Cardiovascular and Medical Sciences


Prof Mandy MacLean

(
Mandy.MacLean@glasgow.ac.uk
)

Prof Rhian Touyz

(
Rhian.Touyz@glasgow.ac.uk
)

Title:

Vascular reactivity in a gender specific model of pulmonary hypertension

Mini
-
Project
:

We have demonstrated that the diet pill dexfenfluramine can induce pulmonary
hypertension in mice, but only in female mice. Here we
will examine isolated
pulmonary vascular reactivity in pulmonary arteries from male and female mice
treated with dexfenfluramine. This will involve in vivo techniques as well as learning
small vessel wire myography to examine vascular reactivity. Vessels f
rom Dfen
treated male and female mice as well as naive mice will be examined for their
responses to vasoconstrictors such as serotonin, endothelin
-
1 and noradrenaline.
The acute effects of dexfenfluramine, oestrogen, 16a
-
OHE1 and other oestrogen
metabolite
s will be studied. The student will also examine lungs for the expression
of oestrogen receptors and key signalling elements using western blotting and
RTPCR if time permits.

Area:

Other World
-
Class Biosciences


Institute of Biodiversity, Animal Health
and Comparative Medicine


Prof Neil Evans

(
Neil.Evans@glasgow.ac.uk
)

Dr Jane Robinson
(
Jane.Robinson@glasgow.ac.uk
)

Title:

Peripubertal hormones and male
cognitive development

Mini
-
Project
:

When puberty is blocked by chronic treatment with a GnRH agonist, in males, risk
taking and heart rate variability (a quantitative measure of physiological stress) are
increased and psychophysiological motoric activity (a combined measure of the
psychologi
cal and physical response to a stressful situation) was altered when
studied at both 28 and 48 weeks of ages. These results indicate that pubertal
hormones have significant effects on the development of cognitive reasoning and
behaviour. The results in th
emselves, however, do not delineate between higher
central effects of pubertal hormones on alterations within the structure and
function of the hypothalamo
-
pituitary
-
adrenal ie neuroendocrine stress axis.
Anatomical data would suggest that GnRHa treatment

in these same lambs is also
associated with alterations in adrenal gland structure and molecular data suggest
effects on markers of adrenocortical function. This mini
-
project will further analyse
behavioural data collected when animals took a risk taking

test at 48 weeks of age
to look for effects of GnRHa treatment in male and female lambs and with a variety
of bioimaging techniques including bright field and fluorescent microscopy coupled
with immunocytochemistry will investigate whether there are funct
ional changes in
the corticotrophes within the pituitary glands of animals that received chronic
peripubertal GnRHa treatment and controls. This study is possible as tissue were
banked from the animals that underwent the risk taking experiments upon
concl
usion of the in vivo experiments.

Area:

Ageing


Dr Barbara Helm

(
Barbara.Helm@glasgow.ac.uk
)

Dr Ruedi Nager

(
Ruedi.Nager@glasgow.ac.uk
)

Title:

Chronotype

as a constraint in response to novel environmental conditions


BBSRC Mini
-
Projects 2012

Mini
-
Project
:

Coping with novel environments is an emerging concept in assessing welfare and
functioning of animals in a changing world. This is relevant both to studies of
animals in
captivity as well as in natural environments. A particular challenge is to
apply these concepts to free living animals in an increasingly altered environment. A
change in environment is only detrimental to an animal if the animal cannot
adequately respond
to the challenge. Therefore, a primary goal in research of
animal health is assessing the impact of environmental change on organisms in
relation to their coping ability. So far, little consideration has been given to the
ability of organisms to keep pace
with novel conditions across the 24h day. In
general, animals have to acquire sufficient resources for full physical functioning
and allocate them to diverse processes across the day. The challenges of acquisition
and allocation depend in part on temporal
conditions, and optimal scheduling of
these activities depend on environmental conditions, such as altered temperature
or food availability or disturbance.


Animals may be able to respond to changes in environments by changing the
scheduling of their activ
ities within the 24h day. However, for proper functioning of
an organism its internal clock must set a reliable pace for its schedule while
retaining flexibility to respond to the changing conditions in natural environments.
From humans we know that when t
heir schedules are shifted e.g. through shift
work or jet lag, this can be associated with major deficits and reduced well
-
being. In
humans as well as in animal models, modified timing and circadian disruption are
known to lead to severe health impediment.

Under natural conditions, the timing of
internal body clocks relative to external timing cues can be measured by recording
the daily change in body temperature. This provides a reliable marker for state of
the clock, and reflects differences in "chronotyp
e" (i.e., a preference for getting up
early or late in the day, respectively).

This project will test the hypothesis that animals that are forced to prolong the
period of activity are constrained to do so by their chronotype. It will focus on wild
great ti
ts Parus major, a model species whose ecology is particularly well know and
will have access to a population of ca. 50 breeding pairs around SCENE (the
university’s filed research station). A pilot study in 2011 showed that it is feasible to
measure wild g
reat tits’ chronotype using tiny state
-
of
-
art data loggers that
continuously record body temperature and activity. The project will extend the
length of the birds’ working days when they provision dependent young in the nest
by increasing the number of you
ng they have to feed. We expect that individuals
with a longer chronotypes measured before the manipulation will show a stronger
increase in provisioning of experimentally enlarged broods compared to individuals
with shorter chronotypes. This would demonst
rate the importance of the expanding
field of chronobiology in understanding animals ability to cope with environmental
challenges
.

Area:

Food Security


Rowland Kao (
rowland.kao@glasgow.ac.uk
)

Title:

The impact of contact structure on phylogenetic tree structure for infectious
diseases.

Mini
-
Project:

The evolutionary analysis of phylogenetic data does not usually take into account
the contact structure underlying the transmission of infectious diseases, though
there is an increasing awareness its importance. Using a series of simulation models
based on

identified abstract contact structurs (e.g. small world network, scale
-
free
network, spatially clustered transmission, etc.), you will simulate disease
transmission models with an imposed mutation model, and explore the implications
of these structures fo
r measures of tree structure (e.g. tree balance, depth,
symmetry), and interpret them in the context of existing trees generated for
Mycobacterium bovis in British cattle and badgers. M. bovis is the causative agent
of bovine Tuberculosis, a disease of imp
ortance for reasons of economics and
animal and human health.

Area:

Other World
-
Class Biosciences


Prof Neil Metcalfe

(
Neil.Metcalfe@glasgow.ac.uk
)

Title:

Links between whole organismal and cellular
senescence

Mini
-
Project
:

As animals age they appear to show deterioration in a broad spectrum of traits,
ranging from the level of damage to particular molecules, through reduced
efficiency of individual organs to impaired performance at the whole
organism level.
However, most such studies are correlative (usually because it is logistically easier
to compare individuals of different ages, rather than track changes within the same
BBSRC Mini
-
Projects 2012

individual over time), and most only examine changes at a single level

of
organisation (i.e. cellular or whole
-
organism senescence, but not both). By using a
study system (the three
-
spined stickleback) in which senescence can be
documented within individuals over a short time period this project will aim to
relate temporal d
eterioration in performance of the whole animal (in swimming
performance, metabolism and sexual attractiveness) to changes at the cellular level
(i.e. levels of oxidative damage to proteins and lipids). As well as providing
important information on the lin
kage between rates of ageing at different levels of
organisation, this project will provide a very broad training in assays of senescence
ranging from the cellular to the whole organism, as well as in experimental design,
reproductive biology and fish biol
ogy.

Area:

Ageing


Dr Ruedi Nager

(
Ruedi.Nager@glasgow.ac.uk
)

Title:

Assessment of animal health and welfare

Mini
-
Project
:

An animal in good welfare is expected to be able to cope with the challenges of the
environments in which it lives. There are a number of approaches using behaviour
and physiology to assess welfare but different approaches may come to different
conclusions
. Animals may appear to cope with their environment when considering
their behaviour, but they may only be able to maintain their typical behavioural
routines at a cost to their physiological machinery. The accumulation of these costs
may negatively affect

the functioning of the body and eventually to ill health or
death. One of these negative physiological feedbacks is chronic stress. A chronic
elevation of energy expenditure may also lead to detrimental effects on the body
through excessive oxidative dama
ge. In this project I propose to compare oxidative
damage in different tissues of birds that had normal energy expenditure through
their live compared with individuals which had a significantly elevated energy
expenditure.


Area:

Food Security


Institute of Cancer Sciences


Dr Kamil Kranc

(
Kamil.Kranc@glasgow.ac.uk
)

Title:

The role of TRIB2 in Haematopoietic Stem Cell (HSC) function and ageing

Mini
-
Project
:

As the population ages and people live longer it is essential to develop strategies to
regenerate failing organs and to treat age
-
related disorders. We study haemopoietic
stem cells (HSCs) as a tractable model system that serves as a paradigm for many
type
s of somatic stem cells that can be utilised for the purposes of regenerative
medicine.


Because of its therapeutic potential, metabolic regulation of stem cells has recently
attracted major scientific and commercial interest. We found that HSCs lacking a
n
essential Krebs cycle enzyme expand dramatically. Since expansion of HSCs and
other somatic stem cells is essential for the success of regenerative medicine we
propose that the pathways we will identify will allow to provide sufficient number of
stem cel
ls for many therapeutic purposes. This project will identify the key
pathways regulating stem cell expansion.


Our normal and malignant haemopoiesis laboratory consists of 4 experienced
postdoctoral fellows and 3 PhD students. We have expertise in in vivo

mammalian
biology and this project will allow to obtain extensive training in this area.

Area:

Ageing


Dr Paul Shiels

(
Paul.Shiels@glasgow.ac.uk
)

Title:

Understanding bio
-
ageing in
healthy tissue as a
determinant of functional capacity

Mini
-
Project
:

We have established that using renal allografts as a source of healthy tissue is a way
to determine key factors involved in health ageing that impacts upon organ function
at a later date. In so doing, we c
an trace, retrospectively, the impact of bio
-
ageing
on healthy tissue function, independently of chronological age and disease. We
have recently demonstrated CDKN2A transcript level, is one such factor that is
superior to both chronological age and telomer
e length ( a proven biomarker of
ageing) in this respect. We have already, in small scale pilot studies identified
several miRNAs, involved in the epigenetic regulation of the CDKN2 locus, also
function in this capacity. The involvement of other forms of e
pigenetic regulation is
undetermined. We propose to evaluate two other forms of epigenetic regulation in
this context, namely (i) methylation of the CDKN2 locus in relation to allograft
function and (ii) long non coding RNAs for association with healthy t
issue function.
BBSRC Mini
-
Projects 2012

These investigations will be undertaken in a pre
-
existing cohort of pre
-
transplant
renal allograft biopsies, alongside CDKN2A, its associated transcript variants and
telomere length. Such analyses will confirm the impact on biological agein
g and
investigate potential determinants responsible for the inter
-
individual variation in
ageing. The cohort will be supported with full clinical and biochemical databases. In
addition to providing superior information on molecular requirements for health
y
ageing, this study will allow better clinical management, enhanced graft survival and
an increased donor organ pool, with direct patient benefit and survival.

Area:

Ageing


Dr Adam West (
Adam.West@glasgow.ac.uk
)

Title:

Understanding chromatin remodelling events at gene promoters

Mini
-
Project:

All eukaryotic gene promoters share a remarkably similar chromatin organisation
when they are undergoing, or are primed for, transcription. The tr
anscription start
site is typically depleted of a nucleosome and is flanked by two tightly positioned
nucleosomes that contain the variant histone H2A.Z. The mechanistic role of these
nucleosome arrangements and the factors responsible are undetermined. Us
ing
ChIP
-
seq, we have identified transcription factors that specifically bind within the
nucleosome depleted regions of active promoters. Using mass spectrometry, we
have now identified several chromatin remodelling complexes that interact with
these trans
cription factors. We are interested to know how these chromatin
remodelling complexes are recruited to gene promoters and what role they play in
establishing promoter architecture and activity.


In this mini
-
project, you will determine whether a particular

transcription factor we
have identified is required for the recruitment of chromatin remodelling enzymes to
a variety of human gene promoters. You will use chromatin immunoprecipitation
(ChIP) assays on cultured human cells that have normal and reduced le
vels of the
transcription factor following RNAi. If your assays are successful and robust, your
data will be incorporated into a publication. You will gain experience in mammalian
cell culture, lentiviral vectors, ChIP and real time qPCR. You will also be
given
training in genome browsing of publically available epigenomic data.