Molecular mechanisms of eukaryotic ribosome biogenesis

我们的目标是确定当受到干扰时会导致危及生命的血液癌症（如骨髓增生异常和急性白血病）发展的途径。我们的长期目标是利用这些信息来设计治疗这些毁灭性血液癌症的新方法。最近令人兴奋的数据将遗传和获得性血癌的起源与我们细胞中所谓的“管家”过程中的缺陷联系起来，特别是在制造蛋白质的机器（称为核糖体）的组装中。我们工作的一个主要重点是详细了解核糖体是如何从其组成部分组合在一起的。为了做到这一点，我们正在了解一些关键蛋白质的三维形状，并试图了解这些蛋白质如何共同组装成熟的核糖体。除了在试管中进行实验外，我们还使用一系列模式生物来确定活细胞中特定核糖体组装因子的作用。我们希望获得的基本见解不仅将提供对核糖体组装过程的基本机制的更深入理解，而且还将有助于改善受核糖体合成障碍影响的患者的诊断和长期前景，更普遍的是，受癌症影响的患者。

We aim to identify pathways that when perturbed result in the development of life-threatening cancers of the blood such as myelodysplasia and acute leukaemia. Our long term goal is to use this information to design new approaches to the treatment of these devastating cancers of the blood. Recent exciting data link the origins of inherited and acquired forms of blood cancer to defects in so-called "housekeeping" processes in our cells, specifically in the assembly of the machines (called ribosomes) that make proteins. A major focus of our work is to understand in detail how ribosomes are put together from their component parts. To do this, we are learning about the three-dimensional shape of some of the key proteins involved and trying to undersrand how these proteins work together to assemble mature ribosomes. In addition to experiments in the test tube, we are also using a range of model organisms to determine the role of specific ribosome assembly factors in living cells. The fundamental insights that we hope to obtain will not only provide a deeper understanding of the fundamental mechanisms underlying the process of ribosome assembly, but will also help improve the diagnosis and long-term outlook for patients affected by disorders of ribosome synthesis and, more generally, for patients affected by cancer.