Tissue engineering commonly uses scaffolds that aim to mimic the structure of biological tissues; however, the scale and geometry of current approaches are dissimilar to those found in nature and these differences hamper the scaffolds' ability to support and control cell behaviour. A recent technological innovation however has led to a demonstrable advancement in producing scaffolds that possess appropriate scale and tailorable geometrical features. This state-of-the-art technology is called melt electro-writing (MEW); a high-resolution version of 3D printing where the material is produced from synthetic polymers, the fibre is laid down in defined orientations and geometries and, most importantly, where this fibre is much closer in size to the native extracellular matrix. MEW was invented by my International Collaborator - Prof. Paul Dalton (University of Oregon), and this project focuses on establishing MEW in the UK to allow superior tissue-mimic structures to be created that will then allow us to better study the structural effects of these scaffolds on cell and tissue behaviour. More specifically, this grant focuses on the growth and assembly of specialised tissues known as basement membranes. Basement membranes are an essential tissue present throughout the body. They provide the interaction point between sheets of cells and the underlying extracellular matrix. Here they act as signalling hubs controlling a wide variety of cellular responses including determining the specific cell types that the cells will become, and protecting these cells from the mechanical forces that move through the extracellular matrix. How basement membranes achieve this is through localised and specific differences in their make-up (i.e. composition) and by differences in the way those proteins are assembled (i.e. structure). Whilst the compositional aspects have been widely studied over many years, the structural aspects have only recently come to the fore. Our overarching hypothesis is that the structure of the extracellular matrix in terms of its topography and geometry, stiffness and pore size will each contribute to how basement membranes assemble on top of that matrix. Those differences in basement membrane assembly will then translate into changes in cell behaviour. In this project we will test this hypothesis by determining how the underlying extracellular matrix influences the way that basement membranes assemble and function. This is a large and fundamental question which is central to many aspects of mammalian biology and with potential therapeutic implications for degenerative and age-related health conditions. Robustly testing this hypothesis has historically been hampered by difficulties in producing accurate experimental models where the specific aspects of the extracellular matrix could be independently modified and their contribution evaluated. However, combining MEW with our existing scaffold fabrication technologies, which represents a step-change advancement in substrate production, means we are now able to precisely tailor the characteristics of the scaffolds and then analyse the cellular and basement membrane responses to these scaffolds. Our project therefore has one distinct aim: to create synthetic structures using scaffold fabrication technologies that mimic the physical properties of extracellular matrix topography, geometry and mechanics, and which go on to influence basement membrane assembly and cell behaviour.

How, when and why did people first arrive and settle in the Americas? This puzzle is one that has captured scientific and public imagination, and is the subject of continued debate. The traditional model of 'Clovis First' asserts that the Clovis culture, named after their distinctive stone tools found near Clovis, New Mexico, in the 1920s and 1930s, arrived on the continent around 13,500 BP. These people would have travelled across the Beringia land bridge in Siberia, during a time when sea levels were lowered during the last ice age, and eventually made their way south on the east side of the Rocky Mountains. Recently a growing body of evidence points to a more complex process, with perhaps several waves of migration of different cultural groups. This has led to a situation where there is no consensus on how humans first came to the Americas. The main barrier to addressing this debate, is the scarcity of well-preserved sites and easily datable materials, where we can be sure that what we are dating really does represent human presence. Human skeletal remains from this period are especially rare, and also incredibly difficult to study due to restrictions of the Native American Graves Protection and Repatriation Act 1990 (NAGPRA). However, a more unusual form of archaeological evidence are well preserved in caves: fossilized human faeces, or coprolites. One of the most famous prehistoric coprolites, is a specimen from Paisley Caves, Oregon, dated 14,300 BP; one thousand years earlier than evidence from the Clovis culture. This coprolite is strong evidence for the 'Pre-Clovis' occupation of North America. The coprolite was identified as human on the basis of ancient DNA, but there have been debates over the stratigraphic integrity. This is a problem which continues to underlie much research in this area. We simply do not know the extent to which these molecules are mobile within cave sediments. This is the missing scientific link which prevents the coprolites from being used, unambiguously, to confirm the pre-Clovis hypothesis and solve this long running debate. Our research will make a first attempt to address these problems, by using a novel integration of biogeochemistry and sediment micromorphology - a method successfully developed by the PI and Co-I. Sediment micromorphology can be thought of as an excavation under the microscope. Intact blocks of archaeological sediments are set in resin and turned into slides for viewing under a microscope. This way we can visually examine the processes by which sediments have been deposited, and whether they have been subsequently altered. Combining this with biogeochemical analysis of faecal lipids will enable us to quantify the extent to which these molecules move from their point of deposition . We will conduct this analysis in conjunction with radiocarbon dating of specific chemical fractions - rather than dating all the organic material in a sample, we will date individual chemical fractions within the coprolites. This way we can provide a firm species identification, and simultaneously an unambiguous date for when the coprolite was deposited. Whoever these early settlers were, these unlikely sources of evidence that they left behind contain a wealth of information which we can now access using the novel techniques proposed in this research project. Once we can demonstrate the integrity of the coprolite materials found in the cave and therefore have confidence in the scientific data we obtain from them, we can use the molecules and fossils preserved with the coprolites to reconstruct the diets of these individuals, and the environment they inhabited. By linking this with high resolution radiocarbon dating, we can begin to extend the research potential to look at other questions of scientific and archaeological interest such as the seasonality of cave use; what relationship did these early settlers have with the environment, and how did they utilise the resources available to them?

A primary aim of lava flow research is the development of accurate flow models that can be used to forecast areas of inundation, and to estimate how far lavas will advance before stopping. Lava flows are complex fluids comprising mixtures of crystals, liquid and gas bubbles and, as they flow, they cool and lose volatile species (mainly water and carbon dioxide) that were initially dissolved in the melt at high pressure beneath the surface. Both cooling and degassing lead to crystallisation of the liquid melt, and thus have significant influence on flow advance. Cooling is a major driver of crystallisation, but its effects are mainly restricted to the thermal boundary layers, where it is an integral process in the formation of surface crust and lateral levées. In contrast, degassing is not restricted to boundary layers and occurs throughout flows, with the potential to affect the entire bulk rheology. Although the effects of cooling-driven crystallisation are accounted for in the current generation of lava flow models, crystal growth due to degassing has not yet been sufficiently quantified to allow its incorporation into models. In recent laboratory experiments, we have been able to simultaneously measure degassing and crystallisation for the first time, and we propose to further this research by examining the growth of crystals directly using hot stage microscopy. This will provide the data on crystal sizes, growth rates and morphologies necessary to quantify the contribution of degassing to the overall crystallisation of lavas. Ultimately, these results will allow degassing-induced crystallisation to be accounted for in numerical lava flow models.

Our world is undergoing rapid changes due to human activity. My research has the overarching goals of understanding how these changes will impact ecological communities, and how we may mitigate their effects. To achieve these goals, I will further develop our theoretical understanding of how ecological communities work, and the primary outcome of this project will be to derive and test new predictions for the way biodiversity is structured across different spatial scales. Given the tremendous complexity of a typical ecological community, it is impossible to include every single detail in any tractable analysis. One therefore has to come up with a strategy for keeping only the most pertinent information, so that we may throw away the details that don't matter but still make accurate predictions. Stephen Hubbell's Neutral Theory is the canonical example of this kind of parsimonious strategy, and it makes surprisingly successful ecological predictions while having very few adjustable parameters. One key output is known as the species abundance distribution, which tells us on average how many species we should expect to find with any given population size in an ecological community. However, there are three important spatial patterns for which it is not yet possible to make analytical predictions in Neutral Theory. The first is how this species abundance distribution changes with sample area---for example, we would expect to find more and more rare species as sample area is reduced. But what is the exact predicted form of this relationship? We don't yet know. The second pattern is known as the species-area relationship, which describes precisely how the number of species found should increase with sample area. And the third pattern is known as distance decay, which tells us how many species we should expect two communities to have in common, as a function of their geographical separation. The first theme of my proposed research will use field theoretical techniques drawn from my doctoral background in theoretical physics, in concert with methods developed during my postdoctoral work in ecology. Using this combination of approaches I will generate new, analytical predictions for these three patterns in Neutral Theory, going beyond the computer simulations available thus far. The application of these tools is quite novel in the context of community ecology, and will open up the opportunity for interaction across the life science interface.The second theme of my research will begin to add more complexity to this picture, by considering a phenomenon known as density dependence. The effect of density dependence is that when population size increases in a local region, leading to overcrowding, individuals find it harder to survive in that region and the population size drops back down. I will continue to use tools from field theory, with a particular focus on interacting field theories to analyze this complex problem, and to determine what difference density dependence makes to the three spatial patterns above.Finally, I will test my new predictions against a broad range of ecological datasets, stretching across life's domains, from trees down to microbes. While macroscopic organisms have a long history in ecology, microbial ecology in particular is a much younger field---and yet we know that microbes are essential to many processes in nature. Modern molecular techniques allow us to explore microbial ecology with unprecedented resolution, and with the collaboration of a large network of colleagues I will test my predictions against this data. Confronting my novel analytical methods with new kinds of ecological data will allow me to make draw important conclusions about the rules by which ecological communities play.

Large Igneous Province (LIP) volcanism is associated with extraordinary mantle melting and voluminous eruptive episodes, which have been linked to mass extinctions of life throughout the Phanerozoic. Significant research over the last three decades has brought the extreme nature of these events into focus. But controls on the nature and tempo of recovery, a topic of emerging interest that highlights potential Earth system tipping points and state shifts, remain unknown. Unexpectedly protracted greenhouse conditions and delayed recovery following multiple Phanerozoic LIPs underscore a fundamental lack of understanding, either of LIP magmatic climate forcing processes or global silicate weathering feedbacks. We propose that cryptic LIP outgassing and weathering combine to shape climate and life after the main phase of volcanism. This proposal will support a multi-disciplinary effort combining field observations; high-resolution records of volcanism, climate, weathering, and paleobiota; and numerical modeling to understand co-evolution of solid and surface Earth during perturbation and recovery. We will leverage three powerful natural laboratory LIPs and climate events, building from the youngest and best-resolved, the Columbia River Basalts and Mid-Miocene Climatic Optimum; to the more voluminous North Atlantic Igneous Province, Paleocene-Eocene Thermal Maximum, and Early Eocene Climatic Optimum; and finally to the Siberian Traps, catastrophic end-Permian mass extinction, and early Triassic hothouse. This project will support an interdisciplinary joint U.S.-U.K. project team including two early career PIs and a sustained outreach/inreach effort in northeastern Oregon, the epicenter of Columbia River Basalt volcanism and site of project field work.