PGR Policy, Strategy and Support

This cross-disciplinary studentship emphasises how a creative research investigation into the climatic and tectonic processes operating along Scotland’s Western Seaboard can help to nurture and communicate a sense of the 'deep time' involved in these. This includes the ‘slow’ temporality associated with glaciations, and the ‘quick’ events of storms and flooding, but also organic temporalities, from evolution to settlement patterns. Such an expanded notion of time is crucial if we are to respond to what Dipesh Chakrabarty has termed the sense of ‘historical confusion’ that climate change presents us with. For Chakrabarty, the uncanny spectre of ‘a world without us’ produces a sense of melancholia and helplessness. One way in which this despair might be countered is by imagining ourselves as planetary creatures whose history has always been entangled with a larger natural history. The Natural Sciences provide knowledge of the ‘more than human world;’ however it is increasingly apparent that the Arts and Humanities have a pivotal role to play in this reimagining in the extent to which they offer representations of the human that reflect and produce dominant modes of behaviour.

This studentship investigates:
1. How field-based geochronological dating methods can use cultural artefacts (written and image-based, and oral traditions), ranged alongside physical artefacts (eg. morphologies and sedimentary archives), to outline the extent and impact of particular climatic/tectonic processes along Scotland’s Western Seaboard.
2. How this work can be theorised, contextualised and composed with respect to extant artistic practices and theories of aesthetics.
3. How an appreciation of the 'deep time' involved in Scotland’s changing Western Seaboard can produce 3 site-specific performances/exhibitions such that new narratives of place and alternative histories emerge. The student will draw on geomorphological/archaeological data and techniques as creative resources, and will prompt reflection on new ways of communicating science.

Scotland’s Western Seaboard is undergoing a post-Ice Age isostatic rebound, in addition to an increased
rate of storminess and Anthropocentric land use changes, leading to a complex series of sea/land/air
processes and interactions. The machair system, for example, is a sloping coastal dune-plain formed by
wind-blown shell-sand, sometimes incorporating a grassland (managed by traditional low-intensity
agriculture) to the landward. Later prehistoric and medieval settlements have reshaped these via grazing,
cultivation and artificial drainage, and have in turn been buried beneath the aeolian sands. Songs and
folklore, as well as geoarchaeological evidence, reveal episodes of both slow and rapid flooding. This pattern
of instability extends into modern times, leading to concerns around disappearing lands and forced
resettlement. At the onset of the 21st century, the Western Seaboard has been identified as a ‘climate
change hotspot.’ How do we proceed to ‘place’ ourselves and others, temporally as well as spatially, in such
a dynamic environment?

The studentship will explore this issue via an investigation of deep time. It will revolve around 3 sites across
the Western Seaboard from which:

• Geochronologies will be constructed, using a combination of archival research and material dating, withreference to specific, transformative events
• A creative imaginary that invokes a sense of the spaces and times of the planet (what we call a ‘geopoetics’) will emerge. This will be based on combining field-based methods from performance, geomorphology and archaeology.
• A series of 3 creative outputs will be produced that perform this imaginary for local audiences, alongside a thesis.

Though there is a current urgency to provide cross-disciplinary approaches to complex problems, such as climate change, the relations between art and science have formed one of the most sustained issues in academic debate, from the work of Leonardo to Snow’s ‘two cultures’ hypothesis. Despite a modern-day institutional compartmentalization that seeks to distance the arts – and the humanities of which they are a part – from the natural sciences, they revolve within a shared history. Profs Lavery and Dixon’s research is concerned with understanding this shared history, and the current dynamics of art/science collaboration, focusing specifically on: the wider contexts that encompass settings for interaction; the scientific research undertaken and the disciplinary, technological, and regulatory contexts that surround it; and the work of the artists, in terms of genre, medium, message, technology, senses, access and dissemination. When the research of Prof. Bishop and Dr Brophy is taken into account, the student will benefit from a unique collaboration of academic interests and world-class expertise.

In addition to producing academic and creative work that takes forward these art/science debates, the student will gain valuable experience in working with academic and non-academic partners, organising, initiating and making publicly accessible artworks, and developing and creating sustainable networks with a range of possible funding bodies, including Creative Scotland, Ecoarts Scotland, Glasgow Life and Cape Farewell. This will benefit the student’s future career path and provide a number of possible routes into both academic and creative-industry based employment. Finally – and importantly – the project provides unique, highly valued cross-disciplinary training that combines field-based techniques from the arts, Earth Sciences and archaeology. From the vantage point of this present, this cross-disciplinary methodological expertise will prepare the student to take advantage of what will certainly be one of the dominant research imperatives of academic and arts-based funding bodies in the next decade or so.

The aim of this project is to develop a minimal synthetic protocell that can report on inorganic and organic substances in water, soil or body fluids. Using a synthetic biology approach (synbio), the student will introduce a light-powered rhodopsin pump into the membranes of protocells made out of robust polymers (polymersomes) generated at high throughput on a microfluidic platform. The electrochemical potential created across the membrane will be used to energize proton-coupled uptake of the targeted substance (e.g. a heavy metal or a disease-related peptide) through a selective cotransport protein, and the resulting internal pH change will be monitored with a pH-sensitive dye. This multidisciplinary project will exploit cutting-edge technologies from photo-biochemistry and biological engineering for a synthetic biology approach to bio-diagnostics. Alongside the laboratory work, the student will critically assess the technology under the responsible innovation (RI) AREA (Anticipate, Reflect, Engage, Act) framework. In this way, the project will develop with an increased awareness of the potential merits of the different uses and any related social constraints.

Background:

Synthetic biology assembles biological parts into new processes such as metabolic or transport pathways. The toolbox is rapidly increasing and so are the applications, but there is still a wide gap between theory and practice. Even in a simple bacterial cell the regulatory network controlling substrate-product relationships is so complex that efforts to integrate new biological functions are often ‘lost in translation’. The success of synthetic biology in the long run will depend on radical simplification of chassis. As an alternative to the top-down approach, which aims to reduce existing biological systems, this project follows a bottom-up approach, adding biological parts to a minimal artificial chassis to achieve the desired biological function. The student will develop a generic solution which should open a window of opportunities for downstream applications in medicine, agriculture and water treatment.

Methodology:

The group of Prof. Amtmann (MVLS, MCSB) has already established an E.coli system to produce recombinant functional halorhodopsins and other ion transporters. In a first step, lipid patches containing the recombinant proteins, extracted from E.coli, will be integrated into polymersomes, manufactured using a microfluidic platform in the lab of Dr. Reboud (Biomedical Engineering). In the longer term, we will explore synthesizing all parts within a cell-free expression system inside the protocells. The student will tag the proteins with fluorescent LOV domains developed by Prof. Christie (MVLS, collaborating with Amtmann), and use a microfluidic fluorescence sorter to separate protocells that have integrated the proteins in the correct orientation. A range of parameters (e.g. concentrations, surfactants, flow rates) will be systematically optimised following a molecular evolution strategy pioneered by Prof. Cronin (School of Chemistry, collaborating with Reboud). Sensory function of different transport modules will be tested by measuring pH profiles of the protocells in response to treatment with range of substrates and concentrations. The functionality of the protocells will be benchmarked against in vivo systems (cyanobacteria, yeast) expressing the same synthetic transport modules. Potential applications and public acceptance issues will be explored through a combination of literature and web resources.

Training and supervision:

The project provides excellent interdisciplinary training opportunities. The student will receive training in molecular biology, biophysics and biochemistry. They will learn how to use the microfluidic platform, and how to systematically optimise molecular devices. The student will also receive guidance on how to access and evaluate publicly available data on regulatory policies, market requirements and public and stakeholder opinion. In addition to shaping the trajectory of the technology, this will equip them with additional skills that are increasingly important in the workplace. In parallel to the project-specific training, the student will be able to pick relevant courses form the RTP of all three colleges. The student will be integrated into a vibrant laboratory shared by Prof. Amtmann and Prof. Blatt. Housed in the Bower Building the lab has state-of-the-art facilities for protein biochemistry, electrophysiology and confocal microscopy. The student will be part of a highly motivated cohort of post-docs and post-grads, many of them working on related topics (e.g. using halorhodopsin for biodesalination and carbon enrichment strategies, EPSRC and BBSRC funded grants). The group meets for weekly lab seminars and journal clubs providing opportunities for the student to present their results and critically discuss scientific papers. Dr. Reboud shares cutting-edge technological know-how and facilities with the group of Prof. Cooper in their superbly equipped laboratory in the Rankine Building. The student will collaborate with the RA/PG cohorts of the Reboud/Cooper group and of the Murphy group, and participate in relevant seminars in the Schools of Engineering and Interdisciplinary Sciences. The ‘Water @ Glasgow’ group will provide a particularly stimulating forum for interaction.

Amtmann lab: http://psrg.org.uk/meet-the-team/

Institute MCSB: http://www.gla.ac.uk/researchinstitutes/biology/

Water @ Glasgow: http://wateratglasgow.org/

The challenges posed by big data are the new reality across scientific disciplines. The shear volume of
new data being produced calls on researchers to completely reorient their approach to the most
important problems, from genomics to astronomy, from particle physics to economics. New analytical
tools are required in order to make progress, as well as a deliberate conceptual shift away from
discipline-specific formalism and conventions. For example, recent advances in high throughput DNA
sequencing technology have revolutionised our ability to quantifying how genes are expressed at
cellular, biological, and evolutionary scales. However, the tools for analysing the resultant big data
from such transcriptomics studies have not kept pace. From a biological perspective there are two
major shortcomings of the present toolkit: i) Differential gene expression is analysed in a gene-bygene
approach, which impoverishes statistical power and is biologically unrealistic because
expression is massively co-dependent; ii) Gene network approaches are implemented within the
context of model laboratory study species and therefore novel information available from non-model
systems (i.e. systems in nature) is not incorporated.

The current project aims to overcome these limitations by applying ideas from topology – a branch of
mathematics that is specifically adapted to treat qualitative properties such as connectivity. Indeed,
this is an area that promises to make impact in big data problems; topological data analysis is among
the latest fast-growing areas of research. This is a genuinely new area to apply a range of tools
developed within pure mathematics to a tractable and important problem in biology. Since the
expression of genes in an organism are co-dependent, co-varying and continuous, treating data from a
topological viewpoint can reveal new relationships by – perhaps paradoxically – deliberately ignoring
structure from conventional modes of traditional analysis.

This project will represent an innovative collaboration in two important ways: i) By making use of a
concrete problem from biology we will have a means of adapting and developing the most recent tools
from topological data analysis; and ii) by appealing to these tools we will seek to revolutionise our
understanding of gene expression and, by extension, the mechanics of organismal biology and
evolution. At the same time, the project is crucially and deliberately aligned with Britain's commitment
to being a world-leader in big data.

Topology is uniquely suited to tackling big data problems: This is a branch of mathematics that is
coordinate-free by design, and as a result it is not biased by existing structure. Gene expression, as a
transcriptome, is the bridge between the genome and the organismal phenotype. RNA-seq technology
is a major advance in elucidating the complexity of this bridge because it can be conducted at any
biological scale, is unbiased, and can be used in medical and veterinary or ecological and evolutionary
contexts. However, these advantages have not been exploited with the existing analytical toolkit, in
part due to the challenge of deriving signal from the vast amounts of data produced. The current
project will develop new analytical approaches to this problem using methods from topology.
For example, given a transcriptomic data set associated with replicate fish populations, one might like
to distinguish those members that occupy different physiologies, morphologies, and ecological niches.
In effect, the data set contains distinct disconnected components (i.e. transcriptome-wide differential
gene expression) that one would like to identify as relevant to the early stages of evolutionary
divergence. Here, the convergent evolution of fish into different niches is a rigorous experimental
design that increases the power of inference for ‘omics in environmental context. We will exploit
algebraic tools in topology designed to identify and characterise the connectivity of these components.
These will be refined in close and iterative consultation with the biological context as the intricacies are
expected to scale with the transcriptomic dimensionality.

This project is intensively interdisciplinary: The ideal candidate will have a strong background in
mathematics specifically and a diverse interest and some experience in the experimental and
biological sciences more generally. In addition, the desire to engage with existing techniques in
statistics and computer programming will be an asset.

The Scholar will be primarily based in the Department of Mathematics and Statistics positioned, in
particular, within the geometry and topology team as part of the Pure Mathematics Group so as to gain
specific training in algebraic topology. This is a dynamic research team, and the scholar will actively
participate in department seminars and liaise with relevant visiting scholars. Additional training will
come by way of the Scottish Mathematical Sciences Training Centre. Most appropriate streams will
likely be topology, algebra, and applied mathematics methods.

The Scholar will also be closely tied to the biological aspects of the project through Elmer and
IBAHCM. New data will be developed for this project and the Scholar will receive hands-on training in
associated molecular techniques (sample handling, RNA extraction and quality control, principles of
RNA-seq). All laboratory support, equipment, and expertise are available. Specific training in
bioinformatics analysis and skills augmentation will be made available locally through Glasgow
Polyomics and/or Edinburgh Genomics programmes and nationally through Wellcome Trust courses.
In addition to providing networking opportunities, such bioinformatics and computational biology
training will provide key skills for the Scholar and open a variety of future research and employment
avenues.

The Scholar will receive training in essential skills such as results dissemination, public speaking and
scientific presentations (supported and mentored by both PIs) in addition to the great breadth of core
skills offered by the Graduate School.

The Scholar will be supported in a variety of avenues of professional development, networking, and
results dissemination. Regional opportunities for presentation and feedback exist through
‘NextGenBUGs (Scotland’s bioinformatics user group) that meets quarterly and of which Elmer is a
participant. Additionally, we request funding for one national (e.g. Population Genetics Group, British
topology meeting) and two EU/international conferences (e.g. Society for Molecular Biology and
Evolution, American Mathematical Society joint meetings) in the final two years.
While the overall project, as outlined, is quite ambitious in its approach to a vast multi-disciplinary
problem, we will have well-defined and meaningful initial goals. In the first instance, our aim will be to
guide the Scholar’s understanding of topological techniques for data analysis in the presence of the
current understanding in gene expression, with the aim of recovering known behaviour by new
(topological) means. This first step will ensure groundbreaking, important, publishable results. It will
provide an essential jumping-off point when approaching new data sets and/or problems, thus ensuring the long-term sustainability of the project.

We are regularly exposed to microbial communities through our drinking water supply. These microbial communities undergo a mass migration from the drinking water treatment plant thorugh the water distribution system and into our built evironment (eg homes, schools, offices, hospitals). In fact every litre of safe drinking water may have up to tens of millions of diverse microbial cells. Over

the last few years, increasing number of studies have utilised state-of-the-art DNA sequencing to
identify the types of microorganisms that survive and even proliferate in our drinking water supplies.
These studies have shown that approaches towards water treatment and distribution have a strong
impact on microbial communities that customers are exposed to through routine drinking water use.
For example, maintaining a disinfectant residual in the drinking water distribution system is a common
strategy for minimizing biological regrowth in most of the world. In contrast, water utilities in some
countries control biological regrowth by limiting the availability of substrates for microbial growth and
thus do not maintain a disinfectant residual. Long-term implementation of these two distinct
approaches for controlling biological regrowth, undoubtedly have an impact on the types of
microorganisms that survive and proliferate in the water supply network.

The central goal of this project is to identify how different approaches to control biological regrowth
(disinfection vs no-disinfection) have influenced microbial community composition in drinking water
supplies. This project will involve a comparative analysis of microbial communities in drinking water
systems in disinfected and non-disinfected systems. This project will not only reveal the identity of
drinking water microbes, but also utilise metagenomic approaches to reveal their functional potential.
The outcomes of this project will provide a platform to debate the risks and benefits of one the central
approaches for the provision of safe drinking water: disinfection.

This project will generate a debate centred on the risks and benefits of water disinfection. A few
European countries have stopped water disinfection and in doing so eliminated risks associated with
carcinogenic disinfection by-products in water supplies. Yet, in most of the world, water disinfection is
considered a necessary evil. We hypothesize that the eliminating disinfection will not increase
pathogen risks in drinking water systems. In fact, our recent study suggests that long-term water
disinfection selects for microbes with antimicrobial resistance traits. We will test our hypothesis
through a comparative microbial analysis in disinfected and non-disinfected systems utilising state-ofthe-
art metagenomics methods. Water utilities in countries that disinfect (USA, UK) and those that
don’t (Netherlands, Belgium) have agreed to collaborate on this project.

Our goal is to encourage the scholar to shape multiple aspects of the project to ensure that they
complete an excellent PhD and emerge as an expert in antimicrobial resistance in drinking water
systems. The research team of AP, UI, and JW will set the initial problem for the scholar – the link
between water disinfection and antimicrobial resistance, and provide the appropriate expertise and
support to ensure that the Scholar excels in her/his PhD project.

S/he will be trained on diverse and cutting edge technologies in molecular microbiology, DNA
sequencing, bioinformatics tools and pipelines, data management. Further, the scholar will closely
collaborate with water companies in USA, UK, Netherlands, and Belgium on selection of specific
drinking water systems that are ideal for this study. As a result, the scholar will not only develop
unique expertise in laboratory based methods, but due to the extensive site selection phase of this
project (which will be in collaboration with water companies) will also develop broad expertise in
drinking water treatment technologies.

The scholar will be exposed to, and develop expertise in Responsible Innovation (RI), a skill set that is
increasingly vital to scholarship in the 21st century. We will provide a supportive environment in which
the scholar can develop skills in public and stakeholder engagement, science communication and
policy analysis. The researcher will benefit from the extensive networks that the School of
Interdisciplinary Studies has fostered with the Scottish government water industry team, research
intensive SMEs, water regulators and representatives of water consumers in Scotland. The scholar
will be embedded in these networks, enabling two central components of the EPSRC RI framework to
be explored, that of anticipation and reflection on the potential impacts of the research, enabling
better alignment with public and stakeholder values, leading to a sustainable impact on the water
sector.

The problem: Endemic diseases of livestock cost the UK agricultural industry an estimated £600m a year. These diseases are transmitted between farms either: a) via purchased livestock, b) directly between animals at field boundaries/shared pastures, or c) indirectly via watercourses, wildlife reservoirs or fomites (e.g. vehicles). Control strategies rely on monitoring by diagnostic tests and vaccination, as well as effective “biosecurity”. Biosecurity, highlighted following the 2001 Foot and Mouth Disease (FMD) outbreak, includes minimising animal purchasing and providing adequate barriers at farm boundaries. However, these measures are not being implemented. Reasons may include lack of awareness of the extent of current disease transmission, lack of faith in the cost-effectiveness of measures, lack of time to implement measures, and sub-optimal communication by advisors.

Aim and objectives: Our aim is to develop a farmer-led control strategy. There are three main objectives: a) to investigate the barriers and facilitators to adoption of control strategies by farmers; b) develop an evidence base on current transmissions that can be presented to the industry; c) to co-develop, with farmers and other industry stakeholders, a farmer-led strategy for further trial.

Methods: The methods bring together social science theory on implementation of new technologies and the development of complex interventions with expertise in molecular epidemiology of pathogens. Three main methods will be applied: a) qualitative interviews, analysed using Normalisation Process Theory, will allow investigation of existing barriers and facilitators to implementation of biosecurity measures; b) analysis of existing evidence of association between prevalence or diversity of endemic pathogens and disease control behaviours on farms, which will inform the design of a prospective field study, targeting pathogens that share transmission routes; c) using data from a) and b) to work with groups of farmers and other stakeholders to co-develop farmer-led control strategies for multiple pathogens that share transmission routes.