The discoidin domain receptors: collagen binding specificity and cooperation with integrins in cell adhesion / migration

我们的目标是研究细胞如何利用一种叫做ddr的特殊蛋白质与胶原蛋白相互作用。当ddr出现故障时，它们可能会导致疾病。希望我们的工作将通过创造可能在抗ddr药物发现计划中有用的试剂来造福人类健康。ddr是治疗包括关节炎和某些癌症在内的许多人类疾病的新型药物靶点。ddr识别胶原蛋白，但我们对这种相互作用知之甚少。当ddr与胶原蛋白结合时，它们将信号传递到细胞中。我们不了解ddr是如何传输此类信息的。胶原蛋白是我们体内含量最多的蛋白质，结构非常复杂。它就像一根绳子，由三条非常长的氨基酸链相互缠绕而成。我们将描述胶原蛋白中被ddr识别的部分。我们将生产与胶原蛋白具有相同绳状结构的合成胶原蛋白片段，并测试ddr使用哪些片段将信号传递到细胞中。ddr并不是唯一与胶原蛋白相互作用的蛋白质。另一种叫做整合素的蛋白质也能结合胶原蛋白。由于ddr和整合素都能识别胶原蛋白，因此很难研究它们对生物功能的相对贡献。我们最近发现，与整合素相比，ddr识别的是胶原蛋白的不同部分。因此，我们可以合成只与ddr结合的胶原蛋白片段，而不是整合素，并利用这些来了解ddr是如何调节细胞功能的。

We aim to study how cells use specialised proteins, called DDRs, to interact with collagen. When DDRs are faulty, they can cause disease. It is hoped that our work will benefit human health by creating reagents that may be useful in anti-DDR drug discovery programmes.The DDRs are novel drug targets for a number of human diseases, including arthritis and certain cancers. The DDRs recognise collagen, but we know very little about this interaction. When the DDRs bind collagen, they transmit a signal into the cell. We do not understand how the DDRs transmit such information. Collagen is the most abundant protein in our body and has a very complex structure. It is built like a rope, composed of three very long strands of amino acids that wind around each other. We will characterise the parts of collagen that are recognised by the DDRs. We will produce synthetic collagen fragments with the same rope-like structure as collagen and test which of these the DDRs use to transmit signals into cells. The DDRs are not the only proteins that interact with collagen. Another type of protein called integrin also binds collagen. Because the DDRs and integrins both recognise collagen, their relative contribution to biological function has been difficult to study. We have recently discovered that DDRs recognise a different part of collagen than integrins. We can thus make synthetic collagen fragments that will bind only DDRs, but not integrins, and use these to understand how the DDRs regulate the cell’s function.