Surveillance of toxic threats by electronic supervision of synthetic neurons in 3D
Surveillance of toxic threats by electronic supervision of synthetic neurons in 3D
批准号:
BB/J020176/1
负责人:
Jeremy Lakey
金额:
$12.77万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2012
资助国家:
英国
项目状态:
已结题
起止时间:
2012 至 --
中文摘要
战斗中的威胁包括释放有毒化学或生物武器。这些相对便宜且容易制作,因此广泛的组织都可以使用。事实上,最近的历史表明,最大的威胁来自小团体,而不是发动常规战争的国家。对于东京地铁使用的沙林神经毒剂和针对美国邮政服务使用的炭疽毒素等已知的例子,可以利用酶分析或免疫分析等现有技术创建高度特异性和敏感性的测试。这与医院实验室用于检测疾病标志物的仪器类似。然而,有可能出现新的工程制剂,而定制的测试还没有开发出来。这些药物可能以多种方式影响细胞,如神经细胞或肌肉细胞,包括阻断特定的电、生化或遗传过程。为了探测到这些威胁,我们需要一个现代的矿工金丝雀,一个能够对威胁做出快速反应并警告人员即将发生危险的生物系统。这里的建议是使用合成生物学方法来创建一个小型化的细胞系统,这个系统很复杂,很可能包含各种毒素的目标位点。读出的是一个快速的电信号。合成生物学将从3个层面进行开发。首先,将利用微技术制作硅片,使神经细胞在其中生长。我们将设计一种电极,它具有类似于神经细胞的纳米技术表面。这将促使细胞紧密地附着在电极上,这将使我们的系统非常敏感,即使它只使用一个记录电极来监听细胞之间的电子交谈。其次,我们将合成新的蛋白质网和支柱来指导神经细胞的生长,使分离的细胞更像人类大脑中的细胞。这将取代围绕在活组织细胞周围的天然支架,稳定细胞并引导其生长。最后,我们将使用来自胚胎干细胞系的小鼠神经细胞,使我们未来能够设计用于新的毒素检测系统的特别敏感的细胞。这意味着这些实验将不使用动物,结果将更加可靠。这个为期一年的项目的结果将证明我们有能力使用微型细胞培养作为一种现场技术来检测对我们的城市和武装部队的有毒威胁。在未来,这项技术可以在医学研究和新药筛选方面有更广泛的应用。
英文摘要
Threats in combat situations include the release of toxic chemical or biological weapons. These are relatively cheap and easily made so that they are available to a wide range of organisations. In fact recent history shows that the biggest threat is from small groups rather than states waging conventional warfare. For known examples such as the sarin nerve poison used on the Tokyo underground and the anthrax toxin used against the US postal service, highly specific and sensitive tests can be created using existing technology such as enzyme assays or immuno assays. These are similar to those used in hospital laboratories to detect disease markers. However there exists the possibility of the emergence of newly engineered agents for which a bespoke test is not yet developed. Such agents may affect cells, such as nerve cells or muscle cells, in a variety of ways including the blocking of specific electrical, biochemical or genetic processes. In order to detect such threats we need a modern day miner's canary, a biological system that can rapidly react to threats and warn personnel of imminent danger. The proposal here is to use synthetic biology approaches to create a miniaturised cell system that being complex is likely to contain the target sites for a wide range of toxins. The read out with be a rapid electrical signal. The synthetic biology will be developed at three levels, firstly a silicon chip will be made using micro technology in which nerve cells will cells will grow. We will design an electrode which has a nanotechnology based surface similar to that of a nerve cell. This will encourage cells to stick closely to the electrode and this will made our system very sensitive even though it uses only one recording electrode to listen in on the electronic chatter between cells. Secondly we will synthesise novel protein nets and pillars to direct nerve cell growth to make the isolated cells more like those in the human brain. This will replace the natural scaffolding which surrounds cells in living tissue, stabilising them and guiding their growth. Finally we will use mouse nerve cells derived from embryonic stem cell lines to give us the future power to design specially sensitive cells for new toxin detection systems. This means that no animals will be used in these experiments and the results will be much more reliable. The result of this one year project will be the proof of principle demonstration of our ability to use miniaturised cell culture as a field technology for the detection of toxic threats to our cities and armed forces. In future the technology can have wider applications in medical research and screening for new drugs.
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