Investigating mRNA methyl cap regulation, function and therapeutic potential

维多利亚·考林在邓迪大学的实验室研究蛋白质是如何在人类细胞中产生的，目的是发现阻止癌细胞和寄生虫生长的新方法。人体由数万亿个具有不同功能的细胞组成，例如皮肤、肌肉、肠道细胞。我们的健康依赖于这些细胞对来自身体的“指令”的快速反应，这些指令是关于它们如何发挥作用，是生长繁殖，是休息还是死亡。通过这种方式，数以万亿计的细胞可以协调它们的活动，形成人体。在癌症中，我们的细胞对这些指令的反应变弱，并以不受控制的方式生长和分裂。结果是大量的细胞聚集，通常形成癌性肿瘤。癌症研究人员调查为什么癌细胞对身体的指令没有反应，目的是开发新的治疗方法来阻止癌细胞的生长。细胞是由蛋白质构成的，因此为了细胞的生长和分裂，需要制造新的蛋白质。在我们的基因中发现的DNA拥有制造蛋白质的“配方”，但它使用一种叫做RNA的信使来为蛋白质提供精确的指令。维多利亚·考林（Victoria Cowling）的实验室正在研究RNA信使是如何在细胞中制造和处理的，以及它是如何被读取以制造蛋白质的。具体来说，考林小组研究了一种被称为“甲基帽”的结构，它标记了某些rna，用于制造蛋白质。他们发现甲基帽可以受到致癌基因的影响，并且某些致癌基因需要甲基帽才能发挥作用。受到这些初步结果的鼓舞，考林小组启动了一项研究计划，调查甲基帽是如何在细胞中合成和调节的，以及这个过程在癌细胞中是如何出错的。他们还与邓迪药物发现部门合作，使用尖端技术寻找阻止甲基帽形成的新化合物。这些化合物可能成为开发新的抗癌疗法的起点。由于人类寄生虫也依赖甲基帽来制造蛋白质，考林博士正与邓迪大学的迈克·弗格森教授合作，研究针对导致非洲昏睡病（一种使人衰弱的疾病，治疗方法仍然有限）的寄生虫布氏锥虫的甲基帽。

Victoria Cowling's lab at the University of Dundee investigate how proteins are made in human cells, with the aim of uncovering new approaches to stop the growth of cancer cells and parasites. The human body is made up of trillions of cells with many different functions, e.g. skin, muscle, gut cells. Our health is dependent on these cells responding rapidly to the "instructions" they receive from the body on how to function and whether to grow and multiply, rest or die. In this way, trillions of cells can co-ordinate their activities to form the human body. In cancer, our cells become less responsive to these instructions, and grow and divide in an uncontrolled manner. As a result masses of cells accumulate, often forming cancerous tumours. Cancer researchers investigate why cancer cells become unresponsive to instructions from the body, with the aim of developing new therapies to stop cancer cells growing. Cells are built from proteins and therefore for cells to grow and divide, new proteins need to be made. DNA found in our genes holds the "recipe" for making proteins, but it uses a messenger called RNA to provide precise instructions for proteins. Victoria Cowling's lab is investigating how the RNA messenger is made and handled in the cell, and how it is read to make proteins. Specifically, the Cowling group investigates a structure called the "methyl cap" which flags certain RNAs to be used to make proteins. They discovered that the methyl cap can be influenced by cancer-causing oncogenes and that it is needed for a certain oncogenes to function. Encouraged by these initial results, the Cowling group has initiated a programme of research investigating how the methyl cap is synthesized and regulated in the cell, and how this process goes wrong in cancer cells. They are also collaborating with the Dundee Drug discovery unit to use cutting-edge technology to look for new chemical compounds that stop the methyl cap from forming. Such compounds may form the starting point for developing new anti-cancer therapies. Since human parasites are also dependent on the methyl cap to make protein, Dr Cowling is collaborating with Prof Mike Ferguson at the University of Dundee, to investigate targeting the methyl cap in the parasite, T. brucei, which causes African Sleeping Sickness, a debilitating disease for which treatment remains limited.