Awaiting Public Project Summary
The Study shall investigate the potential of a new acoustic technology, termed "Sonobiology", to produce and manipulate living cells in culture, under conditions relevant to industrial use. The cells used for the investigation shall be human cells of the type used by industry to evaluate new drugs and test the biosafety of these and many other materials. The acoustic technology shall be applied to cell samples at times when it is necessary to separate living from dead or damaged cells, and the utility of the technology shall be measured in terms of enhanced cell performance when those cells are used in conditions similar to those applied in, for example, preclinical drug discovery. The advantages of acoustic cell manipulation will be assessed not only by improved analytical performance, and also in terms of cost-efficiency gains in processes relevant to commercial laboratory situations, where standardisation and speed of cell handling are critical. If successful, the outcome shall be a proof of principle that acoustic techniques have potential to improve cell-based analysis tools widely used by the pharmaceutical and healthcare industries
Cell-based analysis is a key technology in preclinical development of new drugs and healthcare products. By use of ethically-sourced human cells it is an attractive alternative to, and replacement for, animal testing. There is incentive to make cell-based analysis models as tissue-like as possible, making them 3-dimensional instead of conventional 2D cell cultures. This should confer analysis based on these models with high predictive value, but this increases the technical difficulty, and the time and resource needed to assemble the models. The project will test the feasibility of manufacturing cell-based analysis models by additive printing of both the cells and their supporting biological scaffolds into the multiwell culture dishes typically used in preclinical screening of candidate drugs. A successful demonstration of additive printing in this context will create opportunity to build new cost-effective, automatable manufacturing processes for cell-based systems. This innovation will have significant commercial value in a market sector worth >$2Bn world-wide; it will also increase end-user screening efficiency and, in so doing, reduce new drug development costs and shorten development time.
The Study will test the feasibility of developing a novel collection device for sampling of workplace or domestic environments and testing of the collected samples for their health risk. The sample collector will be designed principally to capture sub-microscale materials that are increasingly part of industrial manufacturing and new products. Sample collection will address an unmet need to evaluate the impact of such materials on human biology. Therefore, sample collection with be followed by sample presentation to an ethically-attractive cell culture system based on cell types able to detect these materials, and provide a measurable response indicating their biosafety risk. Ultimately, the system shall have application in the testing, under laboratory or field conditions, of workplace or environmental samples for nanosafety risk.
The project shall test the feasibility of delivering complex cell culture models as frozen products, assembled in one central facility. These complex cell models are required by industry to answer important questions about candidate drugs during preclinical testing, and also have use in testing of other materials with potential health benefit, such as functional foods or traditional medicines. The complex models shall contain human cells, to enhance their analytical value. They shall be assembled into architectures resembling their tissues of origin: the project example shall be lung cells placed so as to reproduce structures lining the tissue’s airways. The freezing process shall be applied to cells pre-assembled in these structures and not, as conventionally, to cells frozen in bulk. Study success shall make the cell models available to a new commercial audience, and allow discovers to add value to candidate therapeutics before licensing-on to pharmaceutical players.
The project will develop a consistent, highly functional and biologically robust technology for the cryopreservation of cells in microtitre plates. These cells will be used in subsequent screening applications, for example drug safety testing. Many cell types are used for screening applications, with hepatocytes being widely used to investigate drug safety and metabolism in pharmaceutical research. Microtitre plates are used for screening; these plates have either 96 wells (200 µL per well) or 384 wells (25 µL per well). However, with the exception of robust cell types, cryopreservation of cells in microtitre plates is unsatisfactory. A high quality frozen poduct would be disruptive, lowering shipping costs considerably and giving greater flexibility to end users.
The project will build a new tool for the identification of food constituents which can be used to prevent or treat osteoporosis. The new tools will be in the form of a cell culture system which contains human bone cells. These cells will be cultured under laboratory conditions in which they display activities relevant to the development of osteoporosis. These activities will be measured when the bone cells are exposed to new food materials, so that the system identifies those food constituents which may bring health benefit if incorporated into the diet. An important feature of the new test system will be the ability to apply mechanical stress to the bone cells, just as happens constantly in the body. This innovation will encourage bone cells to behave in culture as they do when inside the bone, and in doing so, should make food test results predict accurately their health benefit. In doing so, this new laboratory tool will reduce the need for animal testing of new foodstuffs, and make nutritional trials of functional foods more cost-effective, through early selection of candidates likely to give health-benefit, and de-selecting those destined to fail before major expense is incurred.
This Study will test the feasibility of developing a novel cell-based assay product for use in nanosafety testing. The assay will be built using haemocyte cells of the marine mussel Mytilus, a sentinel species exquisitely sensitive to the presence of environmental pollutants. Haemocytes are readily isolated in large numbers, and can be stored frozen as suspension cultures. These cells possess the biochemical features of cell-mediated immunity, so offering a unique opportunity to screen environmental samples for nanotoxic contaminants. The study aims to incorporate these attractive features into a robust cell-based assay capable of medium-throughput screening, which can become a user-friendly, standardisable analysis tool. If successful, the assay product is likely to find widespread commercial application in the testing, under laboratory or field conditions, of workplace or environmental samples for nanosafety risk.
The project will deliver new tools that can be used to test potential new drugs, food constituents with possible health benefit, and which also offer a new approach to measuring the effect on human health of particles present in our domestic or workplace environment. These tools will be based upon living cells that are placed in situations where they reproduce the function of the lung or the digestive tract surfaces. To measure the response of these cells to challenge by the test materials, the project will, as one of its prime objectives, introduce reporting systems into the cells that allow their state of health and functions to be measured without disturbance, over the duration of an experiment. The proprietary techniques for introducing these reporters will be a prime focus of the project, as will the new cell models that are used to demonstrate the power of the combined technologies. The project outputs will have wide application across the pharmaceutical, food and other industry sectors.
Cell-based analysis is now the preferred method for preclinical testing of candidate drugs, as well as having use in evaluating the biological activity and safety of materials as diverse as traditional medicines, food components and medical devices. This wide utility is prompting development of assay kits that make cell-based assays available to relatively inexperienced operators and those with limited cell culture infrastructure. Delivery of reagents that generate the assay read-out is a critical step in the assay process and should, for optimal assay performance, be synchronised across multiple assay samples and performed without disturbing the cells in culture. This project tests the feasibility of realising these desirable attributes by delivering substrate through release from thermosensitive polymer-based capsules using small, short-term temperature manipulation of the cultures. The technology developed will be applied in a novel panel of cell-based assay kits.
New foodstuffs or food components may, beyond their nutritional value, benefit human health, as with nutraceuticals or functional foods, or may present health risk through contamination at source or during processing. Therefore, there is need to complement chemical analysis of foods with biological screening that assesses health risk or benefit using predictive, easy-to-use tools which are standardisable across test materials and locations. The project will develop a novel system for food safety and health-benefit testing, based on screening for biological responses to food components in human cell-based systems. Analytical power will lie in the use of human primary cells with physiological relevance, in methods for pre-screening complex samples, and in the generation of high-content information using leading-edge molecular technology. The project output will be a transferable service capable of installation in food-based CRO operations and a panel of products enabling out-licensed or third party technology uptake.
Animal nutrition and husbandry for dairy and meat production continue to be the subject of extensive research, for prevention of animal disease, to increase production, and to improve product quality at source. Feed formulation is becoming automated, programmable and customisable for each producer, a process informed by ex-vivo models of rumen fermentation, but impeded by lack of in vitro models that can predict the effect of novel feed supplements, or their metabolites, on animal metabolism and meat or milk composition, which makes expensive, difficult large-animal trials the only option. The project will build bovine cell cultures that reproduce metabolism and product synthesis in vivo, and with it the means to conduct predictive testing of feed supplements, as well as biosafety testing of adulterants or environmental pollutants.
Osteoporosis is a disease affecting the quality and density of bones rendering them brittle and fragile. According to the International Osteoporosis Foundation, 200 million women worldwide are affected. The project will develop a tool, in the form of personalised cell-based analysis, for the screening of individuals pre-disposed to osteoporosis, to enable customised dietary intervention that assists prevention or supports treatment of the disease. The Study addresses directly the Competition focus on new foods with health-promoting properties, and its output creates an evidence-based means of relating genetic predeposition to osteoporosis with cellular functions that, in susceptible individuals, are directly linked to the disease's onset and aetiology.