Overview: We request funds to make measurements of the elapsed time since major earthquakes on active faults in central Italy using 36-Cl cosmogenic dating, and calculate stress transfer from historical/palaeoseismic earthquakes. This will allow (1) knowledge transfer to at-risk communities in the region so they can prepare for future earthquakes if a fault with a long earthquake elapsed time has had stress transferred onto it by a neighboring earthquake(s), and (2) communication of this process to other regions with similar earthquake hazard. Technical Summary: Active faults experience earthquake rupture due to stress transfer from neighboring earthquakes only if the fault in question is close to its failure stress. We lack knowledge of which faults are close to their failure stress and thus cannot interpret calculations of stress transfer in terms of the probability of impending earthquakes. We propose, for an active normal fault system in central Italy, to measure the elapsed time since the last earthquake normalised to fault slip-rates using in situ 36-Cl cosmogenic isotope dating, because this is a proxy for how close a fault is to its failure stress. We will combine this with calculations of stress transfer from historical and palaeoseismic earthquakes in order to calculate which faults have the highest probability of rupture. Background: When an earthquake ruptures an active fault, stress is transferred onto neighboring active faults. This transfer of stress may cause a neighboring active fault to rupture in a subsequent earthquake. For example, the 2004 Boxing day earthquake on the subduction plate boundary near Sumatra caused severe loss of life on that day, but also triggered subsequent earthquakes in 2005, 2007, 2009 and 2010, each of which caused major loss of life. Such triggered earthquakes also occur on active faults within plates, such as the three 9th September > Mw 6 earthquakes in 1349 A.D. in central Italy, which occurred on the same day, but on different active faults; this has increased concern for the possibility of a future mainshock to follow the 2009 L'Aquila earthquake (Mw 6.3) whose ongoing aftershocks have transferred onto a neighboring fault (Fig. 1). A key point is that, despite the above examples, earthquakes do not always trigger subsequent earthquakes. Subsequent earthquakes only occur if the neighboring fault(s) are already close to failure due to long-term loading from motions in the crust or between plates. Identification of such faults could inform local populations and civil protection agencies in advance of a future earthquake allowing location-prioritised mitigation efforts. However, unfortunately, we cannot directly measure stress on a fault at 12-15 km depth where intra-plate mainshocks nucleate and so cannot identify such faults. However, we can measure a proxy for stress-through-time, that is elapsed time since the last earthquake, using cosmogenic isotopes (36-Cl). In the sub-surface, 36-Cl concentrations accumulate through time mainly due to hits on calcium atoms by cosmic particles. With 1-2 m slip in each earthquake on active normal faults, and with knowledge of 36-Cl production rates at depth, 36-Cl concentrations measured at 1-2 metres depth quantify elapsed time since the last earthquake. We can dig trenches to expose the fault plane to 1-2 metres depth and measure 36-Cl concentrations on the fault planes. If a neighboring earthquake has loaded/stressed a location with a high 36-Cl concentration, and hence a long elapsed time, we will be able to inform civil protection agencies responsible for planning mitigation; no such data are available at present. We can make such measurements, and have ongoing links with government civil protection project partners who make the seismic hazard maps for central Italy, and who are involved in communicating seismic hazard worldwide.

Seismic hazard assessment and understanding of continental deformation are hindered by unexplained slip-rate fluctuations on faults, associated with (a) temporal clusters of damaging earthquakes lasting 100s to 1000s of years, and (b) longer-term fault quiescence lasting tens to hundreds of millennia. We propose a new unified hypothesis explaining both (a) and (b), involving stress interactions between fault/shear-zones and neighbouring fault/shear-zones; however key data to test this are lacking. We propose measurements and modelling to test our hypothesis, which have the potential to quantify the processes that control continental faulting and fluctuations in the rates of expected earthquake occurrence, with high societal impact. Our aspiration is that cities and critical facilities worldwide will gain additional protection from seismic hazard through use of the calculations we pioneer herein. The background is that slip-rate fluctuations hinder understanding because they introduce uncertainty about whether specific faults are active or not. For example, a review in Japan of earthquake risk to critical facilities, such as the Tsuruga nuclear power plant (NPP), revealed a geological fault under a nuclear reactor (Chapman et al. 2014). The question that arose was whether the fault was active or not. Japan's Nuclear Regulatory Authority (NRA) has guidelines defining fault activity, and considered the fault under the reactor to be active, evidenced by faulting in sediments <~125,000 years in age. The Japan Atomic Energy Power Company (JPAC) disagreed, following study by an independent team of geoscientists. In 2014, the Tsuruga NPP remained closed due to ongoing debate between the NRA and JPAC, with similar debates ongoing for other NPPs. We suggest that defining fault activity as simply "active" or "inactive" is unsatisfactory because it is debatable even amongst experts. In fact a fault that has not slipped in many millennia may, in reality, not be inactive, but instead may simply have a low slip-rate, with the capability to host a damaging earthquake after a long recurrence interval. Our breakthrough is we think slip-rate fluctuations over both timescales (a and b) are a continuum, sharing a common cause involving interaction between fault/shear-zones. For the first time, we provide calculations that describe this interaction, quantifying slip-rate fluctuations and seismic hazard in terms of probabilities. We show that slip during an earthquake cluster on a brittle fault in the upper crust occurs in tandem with high strain-rate on the viscous shear-zone underlying the fault. This deformation of the crust produces changes in differential stress on neighbouring fault/shear-zones. Viscous strain-rate is known to be proportional to differential stress, so, given data on slip-rate fluctuations one can calculate changes in differential stress, and then calculate implied changes to viscous strain-rates on receiver shear zones and slip-rates on their overlying brittle faults. We provide a quantified example covering several millennia, but lack data allowing a test over tens to hundreds of millennia. If we can verify our hypothesis over both timescales, through successful replication of measurements via modelling, we will have identified and quantified a hitherto unknown fundamental geological process. We will study the Athens region, Greece, where a special set of geological attributes allows us to measure and model slip-rate fluctuation over both time scales (a and b), the key data combination never achieved to date. We know of no other quantified explanation that links slip-rate fluctuations over the two timescales; the significance and impact of accomplishing this is that it has the potential to change the way we mitigate hazard for cities and critical facilities. Chapman et al. 2014, Active faults and nuclear power plants, EOS, 95, 4

This proposal aims to improve estimates of Antarctica's contribution to sea level. Sea level is currently rising at approximately 3mm/yr. If we are to understand why it is rising and how future sea-level rise will continue - perhaps accelerate - and lead to a wide range of societal impacts then we need to understand the different contributions to sea level. Some of the largest contributions come from the great ice sheets in Antarctica and Greenland but the amount of ice being lost from Antarctica is particularly difficult to establish. There are three main ways to measure the amount of ice being lost or gained from Antarctica - its 'mass balance'. These are (i) satellite altimetry (measuring very precisely how the ice sheet surface is going up or down through time); (ii) the input-output method (calculating the difference between estimates of how much snow falls on Antarctica, and how much ice breaks off at the coast or is lost by melting); (iii) satellite gravimetry (measuring minute changes in Earth's gravitational field caused by loss or gain of ice in Antarctica through time). Ideally, these three techniques would provide similar answers but they currently do not. All the techniques have problems or drawbacks and all are the subject of ongoing research. In this proposal we focus on the satellite gravimetry method. Mass balance from gravimetry is particularly tricky to calculate because the changes to the gravitational field are not only affected by ice loss/gain but also by mass moving around beneath the Earth's crust. At the end of the last ice age, a large thickness of ice in Antarctica melted and the rocks deep within the Earth are still responding to this change 1000s of years later. The consequence of this response - which scientists call glacial-isostatic adjustment or 'GIA' - is that the satellite measurements have to be corrected by a very large amount that accounts for movements of the rocky material and thus to provide the 'real' figure for ice mass loss/gain. It is getting this correction right that has been so problematic because it requires us to know the history of the ice sheet (including past snow accumulation) for over 10,000 years and also to know the structure of the Earth underneath Antarctica. Recent projects including a previous one by our group that was funded by NERC have made substantial improvements in determining this correction but our recently published work has shown very clearly that we still lack data to pin down the GIA correction tightly enough in parts of East Antarctica. In other words there is still an unacceptable level of uncertainty in East Antarctica, which leads directly to uncertainty in sea-level contribution. In this proposal we have identified a region called Coats Land, in East Antarctica, which accounts for the greatest remaining uncertainty in the GIA correction but where we have managed to identify suitable sites where we can obtain the necessary ice history information, new seismic measurements of crustal structure, and GPS measurements of crustal uplift (a key part of testing GIA models). By visiting these sites and undertaking some world-leading modelling using our field data and a synthesis of existing snow accumulation data we will provide a new and much improved GIA correction for Antarctica. Whilst our data collection focus will be on Coats Land our subsequent modelling effort will encompass all of Antarctica. The data will be used to develop an improved model of GIA in Antarctica in order to correct the GRACE dataset. We conservatively estimate that with the measurements and modelling that we propose to carry out then we can at least halve the total uncertainty in satellite gravimetry measurements of Antarctic mass balance, and probably do substantially better than this. This proposal raises the prospect of getting an improved estimate of the Antarctic contribution to present-day global sea level rise.

Pluripotent stem cells can differentiate into all adult cell types. Understanding how pluripotent stem cells differentiate into many different mature cell types is a key question for the biomedical and regenerative sciences. The regulation of gene activity is key for stem cells and differentiation. In the nucleus, histones and other molecules wrap the genetic material in a substance called chromatin. The accessibility of DNA within chromatin is of fundamental importance: chromatin "opens" to allow gene activity and "closes" to shut it down. Microscopy studies very early on showed that stem cells have relatively open chromatin while fully mature cells have large closed regions instead. We currently think that pluripotent stem cells achieve differentiation into many different cell types by opening and closing of different regions of their genomes in each type. In the last decade, we have made great advances to understand these opening and closing events in part thanks to the development of techniques that measure chromatin accessibility and interactions across the entire genome, and have elucidated the events that characterize differentiation to a few cell types in vitro. We have also discovered that alterations in these events often lead to cancer and disease. However, we still do not understand how pluripotent stem cells orchestrate their chromatin opening and closing events to unfold the differentiation programs of the myriad of mature cell types that make a complex adult organism. To tackle this question, I propose to measure chromatin interactions and accessibility at the single cell level in the planarian Schmidtea mediterranea, an ideal model organism through which we can investigate pluripotent stem cell differentiation in vivo. Freshwater planarians are invertebrates that, unlike us, have pluripotent stem cells as adults. They constantly differentiate into all cell types to replace damaged cells and to enable the remarkable planarian regeneration properties: each piece from a planarian can regenerate an entire adult in a matter of days. Recent technological advances of single-cell analysis together with the properties of planarians as a model organism enable this research now. We have already implemented single-cell approaches into planarians, resulting in the elucidation of the complete differentiation tree of planarian stem cells. Here I propose to use novel single-cell techniques to measure chromatin structure and accessibility in planarian cells. This will tell us which regions of the planarian DNA and chromatin open or close in every stage of differentiation to each of the major planarian mature cell types. We can also turn off several genes that are likely to be regulating this process and measure chromatin accessibility in these animals. Most of these genes are present in both humans and planarians and we know that stem cells from both need them to function both but we still ignore their precise mechanisms of action. By measuring how chromatin accessibility changes after turning them off we will understand which are the opening and closing events that they regulate and in which cell types they are important. This information will enable new strategies for human stem cell differentiation approaches and regenerative medicine by targeting those same genes. Altogether, this research will allow us to understand how stem cells reshape their chromatin to differentiate into multiple and different mature cell types.