Experimental studies of the mechanism of biological organisation.

关于生物，最难理解的一件事是，它们有能力保持自己的活跃、有组织的状态，而不会筋疲力尽。物理学家期望所有的系统都受热力学第二定律的支配，热力学第二定律指出，系统的无序或称熵总是会增加。对于一个有生命的系统来说，这是一种腐朽、无序和死亡的判决，这是所有生命的命运。然而，热力学允许有序状态继续存在，前提是它保持在平衡状态之外，并且自由能在系统中的流动增加了系统外部的熵。因此，热力学与生物的存在是相容的，但它没有提供任何关于生命系统组织和维持自身的机制的信息。这个研究计划将为一个长期存在且有争议的假设提供几个实验测试，这个假设是在电磁频谱的太赫兹(THz)区域中的极长波长振动模式在生物系统的自组织中发挥着重要作用。太赫兹波的波长约为300微米，在电磁光谱中位于无线电波和红外辐射之间。在生物组织机制中利用太赫兹模式的想法很有吸引力，因为在生物运行的温度下，热能能够激发能量高达6太赫兹的波。因此，生物中的化学相互作用在这个频率范围内激发的旋转和振动模式可能会被进化所选择，在生物组织中发挥作用。一个关键的问题是太赫兹模式是否存在足够长的时间，从而在生物活动中发挥重要作用。详细的理论工作是相互矛盾的，关于长寿命太赫兹模的实验证据也很少，也有争议。解决这个问题需要的是实验。然而，实验室的太赫兹辐射源很弱，功率水平在微瓦到毫瓦范围内，而这些低功率水平是以前无法对这一假设进行令人信服的测试的主要原因。在这个项目中，我们将利用达累斯伯里实验室爱丽丝加速器上独特的高强度太赫兹光束线，该实验室配备了组织培养设施。该光束线具有较高的峰值功率，70kW，较低的平均功率24 mW。高峰值功率在1皮秒的短脉冲中传输。高峰值功率很重要，因为它使我们能够克服太赫兹被水吸收的问题。低平均功率使消除热效应成为可能，而热效应可能对生物系统产生重大影响。最后，如果没有将标本保存在组织培养设备中的能力，一些实验就无法完成。太赫兹辐射可能会影响多个层次的生物组织；分子水平上的直接相互作用可能会影响细胞行为，进而影响细胞与细胞的相互作用，从而影响整个有机体的发育。因此，我们将通过研究以下三个方面来研究太赫兹在生物组织的所有三个水平上的作用：1)太赫兹模式在生物分子相互作用中的作用；2)太赫兹模式对干细胞生长和分化的影响；3)太赫兹模式对斑马鱼胚胎正常发育的影响。最后，为了巩固利物浦大学物理学家和生命科学家之间的研究合作，我们将邀请这个社区的团队提交小规模推测性研究计划的提案。

One of the most difficult things to understand about living things is their ability to maintain themselves in an active organised state without running down. Physicists expect all systems to be governed by thermodynamics the second law of which states that the disorder, or entropy, of a system will always increase. For a living system this is a sentence of decay, disorder and death and that is the fate of all life. However thermodynamics allows an ordered state to continue provided it is maintained out of equilibrium and a flow of free energy through the system acts to increase the entropy outside of the system. So thermodynamics is compatible with the existence of living things but it does not provide any information on the mechanisms by which living systems organise and maintain themselves.This research programme will provide several experimental tests of a long standing and controversial hypothesis that very long wavelength modes of vibration in the terahertz (THz) region of the electromagnetic spectrum play an important role in the self-organisation of biological systems. THz waves have wavelengths of the order of 300 microns and lie between radio waves and infrared radiation in the electromagnetic spectrum. The idea that THz modes are exploited in mechanisms of biological organisation is appealing since at the temperatures at which living things operate the thermal energy is able to excite waves with energies up to 6 THz. Consequently it is possible that rotational and vibrational modes excited in this frequency range by chemical interactions in living things will have been selected by evolution to play a role in biological organisation. A crucial issue is whether THz modes live long enough to be important in biological activity. The detailed theoretical work is conflicting and the experimental evidence for long-lived THz modes is sparse and controversial. What is needed to resolve this question is experiments. However laboratory sources of THz radiation are weak, with power levels in the micro W to mille W range and these low power levels are the principle reason why it has not been possible to carryout a convincing test of this hypothesis previously. In this programme we will exploit the unique intense THz beamline on the ALICE accelerator at the Daresbury laboratory that is equipped with a tissue culture facility. The beamline has a high peak power, 70 kW, and a low average power 24 mW. The high peak power is delivered in a short pulse of < 1 pico second. The high peak power is important because it enables us to overcome the problem of THz absorption by water. The low average power makes it possible to eliminate thermal effects which can have a major impact on biological systems. Finally some of the experiments could not be done without the ability to maintain the specimens in the tissue culture facility.THz radiation has the potential to influence multiple levels of biological organisation; direct interactions at the molecular level have the potential to affect cell behaviour, which in turn will influence cell-cell interactions thereby affecting the development of the whole organism. We will therefore investigate the role of THz at all three levels of biological organisation by studying:-1) The role of THz modes in biomolecular interactions2) The influence of THz modes on the growth and differentiation of stem cells.3) The influence of THz modes on the normal development of zebra fish embryos. Finally in order to consolidate research collaborations between physical scientists and life scientists in the University of Liverpool we will invite teams from this community to submit proposals for small scale speculative research programmes.