Transition Support CDA Raman Das

奖学金目标概述：发育中胚胎脊髓中的新生神经元脱落，以移动到最终位置。由于这种脱落事件，这些新生神经元失去了使它们能够区分前后的关键蛋白质，导致它们失去极性。在此之后，神经元现在必须迅速重新极化自己。这种复极化是至关重要的，因为它允许神经元延伸一个长的细胞过程，称为轴突，它与其目标连接，可能是肌肉或其他神经元。在发育中的胚胎中，神经元对来自周围组织的外部线索作出反应而复极。这些外部线索决定了这种复极化的位置，从而决定了轴突的行进方向，或者决定了轴突是否形成。因此，这是一个关键的事件，是必不可少的功能性神经元回路的形成。我的奖学金将研究指导这一关键细胞生物学过程的分子和细胞机制。除了神经元复极化，许多癌细胞在转移过程中也经历了非常相似的复极化过程，这使得它们能够迁移到不同的位置并形成更多的肿瘤。很可能癌细胞以类似于新生神经元的方式做到这一点，因此了解神经元复极也可能有助于我们了解癌细胞如何迁移形成继发性肿瘤。因此，了解细胞如何响应周围组织而复极化具有深远的影响。迄今为止取得的进展：由于尖端脱落，新生神经元也失去了它们的细胞天线，称为初级纤毛。我们已经证明，由于这种脱落，这些细胞能够停止分裂并进入神经元分化的后期步骤。然而，当这些细胞重新极化时，它们必须能够接收和响应来自周围组织的信号，以使它们的轴突向正确的方向延伸。我们的工作已经证明，新生神经元重新生长一个新的初级纤毛，现在允许细胞对信号环境做出反应，并指导新生神经元的复极和新生轴突的延伸。这项工作最近发表在《科学进展》杂志上。过渡资金如何促进我的职业生涯：我的目标是在申请MRC高级奖学金时处于有利地位。虽然我已经建立了一个独特的研究利基，我需要更多的出版物，使我在这方面的竞争力。过渡资金将使我能够利用这一强大的基础，使我能够保留我的博士后，从而促进在两年的过渡期内发表另外两篇论文，这将巩固我的实验室作为研究细胞如何在组织环境中极化的最佳环境的地位。此外，获得过渡支持将为我提供更大的工作稳定性，因为我将被曼彻斯特大学永久雇用。这种支持也将是我的博士后，谁也打算申请她自己的奖学金，以建立她的独立研究生涯的变革。

Summary of fellowship aims: Newborn neurons in the spinal cord of the developing embryo shed their tips to move to their final location. As a result of this shedding event, these newborn neurons lose key proteins that allow them to distinguish their front from their back, causing them to lose polarity. Following this, the neuron must now rapidly repolarise itself. This repolarisation is crucial, as it allows the neuron to extend a long cell-process, called an axon, which makes connections with its targets, which could be muscles or other neurons. In the developing embryo, the neuron repolarises in response to external cues from the surrounding tissue. These external cues determine the position of this repolarisation and therefore determine the direction in which the axon will travel, or if it forms at all. This is thus a critical event that is essential for the formation of functional neuronal circuitry. My fellowship will study the molecular and cellular mechanisms that direct this key cell-biological process. In addition to neuron repolarisation, many cancer cells also undergo a very similar repolarisation process during metastasis, which allows them to migrate to different locations and form more tumours. It is likely that the cancer cells do this in a way similar to newborn neurons, so understanding neuron repolarisation will potentially also help us to understand how cancer cells migrate to form secondary tumours. Thus understanding how cells repolarise in response to surrounding tissues has far-reaching consequences.Progress made so far: As a consequence of shedding their tips, newborn neurons also lose their cellular antenna, called the primary cilium. We have shown that as a result of this shedding, these cells are able to stop dividing and enter the later steps of neuronal differentiation. However, as these cells repolarise, they must be able to receive and respond to signals from the surrounding tissue to extend their axons in the correct direction. Our work has demonstrated that newborn neurons re-grow a new primary cilium that now allows the cell to respond to the signalling environment and directs repolarisation of the newborn neuron and extension of a nascent axon. This work has recently been published in the journal Science Advances.How transition funding will advance my career: My aim is to be in a strong position to apply for an MRC senior fellowship. Although I have established a unique research niche, I need more publications to make me competitive for this. Transition funding will allow me to capitalise on this strong foundation by allowing me to retain my postdoc, therefore facilitating publication of two further papers in the two-year transition period, which will cement the position of my lab as the best possible environment to study how cells polarise in a tissue context. In addition, being awarded transition support would provide me with greater job stability as I would be employed by the University of Manchester on a permanent basis. This support will also be transformative for my postdoc, who also intends to apply for her own fellowships to establish her independent research career.