Development of magnetic force biotechnology to facilitate neural regeneration

中枢神经系统(CNS)由大脑和脊髓组成，负责协调我们整个身体的活动。这种协调需要数十亿个神经元(神经细胞)的精确连接，有时跨越0.5米长的距离。这些连接是使用被称为轴突的细长纤维建立的，轴突从细胞体投射出来，允许电脉冲在神经元之间传输(有点像连接计算机组件的电路)。中枢神经系统中的神经电路可能是由急性创伤(如脊髓损伤)或在帕金森氏症等神经疾病发展后造成的。在中枢神经系统中，脊髓包含控制复杂运动(如行走)的神经回路。不幸的是，中枢神经系统中的轴突自然再生的能力极其有限，因此由大脑或脊髓损伤导致的功能缺陷可能会无限期地持续下去。目前，全球有数百万人生活在这种损伤的致残影响中，因此迫切需要新的方法来寻找可能恢复这些神经连接的治疗方法。该项目建立在之前成功合作的基础上，利用物理科学和生物工程方法利用远程磁力操纵神经元。在这里，我们将研究是否可以使用磁力方法远程引导轴突重新生长，以重新连接神经回路和恢复功能。为了做到这一点，我们将设计和开发新的可控磁力装置。我们将使用这些系统来靶向装载到轴突内被称为内小体的细胞内的专业微观磁性纳米颗粒。此外，我们还将探索使用先进的基因修饰技术来制备可以在内部生物合成磁性纳米颗粒的神经细胞。为了测试这些方法，我们将研究磁力对一种新的脊髓损伤生物模型的影响，该模型结合了从大鼠皮质和脊髓培养的活组织切片。该项目将汇集一个具有物理和材料科学、神经科学、电生理学、合成生物学和神经外科专业知识的广泛、跨学科的团队。如果成功，该项目将提供所需的关键基础技术，将这些方法转化为脊髓损伤的临床前和最终临床治疗。它还将对神经科学和神经紊乱的其他领域的研究产生重大影响，这些领域寻求在中枢神经系统重新建立回路，例如帕金森氏病。

The central nervous system (CNS) consists of both the brain and spinal cord and is responsible for co-ordinating activity across our entire body. Such co-ordination requires the precise connections of billions of neurons (nerve cells), sometimes across distances of up to 0.5 metres long. These connections are made using long, thin fibres known as axons, which project from the cell body and allow the transport of electrical impulses between the neurons (somewhat like the electrical circuits that connect components in a computer).Damage to the neural circuitry in the CNS can be caused by acute trauma (for example spinal cord injury) or following the development of neurological disorders such as Parkinson's disease. Within the CNS, it is the spinal cord that contains the neuronal circuits that govern complex movements such as walking. Unfortunately, the ability of axons in the CNS to naturally regenerate is extremely limited, and so the functional deficits that result from damage to the brain or spinal cord, can persist indefinitely. Millions of people worldwide are currently living with the disabling effects of such damage, and so new approaches to find potential treatments that could restore these neural connections are desperately needed.This project builds on a previously successful collaboration to use physical sciences and bioengineering approaches to manipulate neurons using remote magnetic forces. Here we will investigate whether magnetic force methods could be used to remotely guide axon re-growth to reconnect neural circuits and restore function. To do this we will design and develop new controllable magnetic force devices. We will use these systems to target specialist microscopic magnetic nanoparticles loaded into intracellular compartments in the axons known as endosomes. In addition, we will explore the use of advanced genetic modification techniques to prepare neuronal cells that can biosynthesize magnetic nanoparticles internally. To test these methodologies, we will investigate the effects of magnetic forces on a novel biological model of spinal cord injury, that incorporates living sections of tissue cultured from the rat cortex and spinal cord.The project will bring together a wide-reaching, cross-disciplinary team with expertise in physics and materials science, neuroscience, electrophysiology, synthetic biology, and neurosurgery. If successful, the project will provide the crucial foundation technology required to translate the methods towards pre-clinical and ultimately clinical treatments of spinal cord injury. It will also have significant impact on research in other areas of neuroscience and neurological disorders which seek to re-establish circuits in the CNS, such as Parkinson's disease.