The structure of amorphous calcium phosphate, a key intermediate in skeletal calcification

这一提议将使我们对骨骼生长过程的理解取得关键性进展。当然，骨骼生长对人类非常重要，因为骨骼形成骨骼，提供机械支持。事实上，骨头是所有脊椎动物的显著特征。人类在进化过程中发展出了制造骨骼的能力，有证据表明它在5亿年前就已经存在了。我们的骨骼是由一种叫做胶原蛋白的蛋白质和一种叫做羟基磷灰石的矿物质的混合物组成的。羟基磷灰石是一种磷酸钙化合物（因此钙在饮食中对健康骨骼的重要性）。像羟基磷灰石这样的矿物质通常是在地质过程中产生的，类似的过程可以用来制造工业中的合成矿物质。然而，身体使用不同的方法来制造骨矿物质羟基磷灰石。大多数人认为骨骼生长仅限于生命的早期阶段。事实上，在我们的一生中，骨骼不断地通过吸收和重组过程进行重塑。(When这些过程发生故障，可能导致疾病，如骨质疏松症。这些过程必然涉及钙和磷酸盐在体内的循环，这些离子存在于细胞间循环的体液中。科学家们已经对骨骼生长有了很多了解。在骨生长过程中，体液中的钙离子和磷酸盐离子沉积在需要新骨的部位。这些离子沉淀形成固体磷酸钙化合物。有趣的是，形成的第一种化合物不是骨矿物质羟基磷灰石。羟基磷灰石是由第一种化合物通过随后的反应形成的。令人惊讶的是，第一种形成的磷酸钙化合物的结构在发现50多年后仍然未知。它被命名为无定形磷酸钙，因为它不是晶体（无定形意味着非晶体）。由于它不是晶体，它的结构无法使用标准方法如晶体学来识别。由于不知道这种化合物的结构，科学家们无法描述骨形成的早期阶段，因此缺少了一个关键的知识。这项建议将通过应用特殊技术来确定无定形磷酸钙的结构来提供缺失的知识。这些技术是科学家们为研究玻璃而开发的技术，例如窗户玻璃，也是非晶体。这些技术包括特殊的衍射实验（类似于晶体学）和计算机建模。这些技术已经成功地揭示了玻璃的结构，但它们在生物学中较少应用于无定形材料，了解无定形磷酸钙的结构将提高我们对骨骼生长的认识。这将带来重要的好处。首先，我们对生物学的理解（包括泌尿系统结石等疾病）。其次，对于那些正在制造生物活性材料的科学家来说，这些材料旨在植入人体并模仿人体自身的骨骼生长过程。第三，对于那些想要找到替代方法来制造矿物的科学家（不使用地质过程）。

This proposal will make a key advance in our understanding of the process of bone growth. Of course, bone growth is very important to humans as bones form the skeleton, which provides mechanical support. In fact bones are a distinguishing feature of all animals which are vertebrates. The ability to make bones developed during evolution and there is evidence that it already existed 500Million years ago. Our bones are made of a mixture of a protein called collagen and a mineral called hydroxyapatite. Hydroxyapatite is a calcium phosphate compound (hence the importance of calcium in the diet for healthy bones). Minerals like hydroxyapatite are normally made in geological processes, and similar processes can be used to make synthetic minerals in industry. However, the body uses a different approach to make the bone mineral hydroxyapatite.Most people think that bone growth is restricted to the early stages of life. Actually, during our whole lives bones are constantly remodelled by absorption and reformation processes. (When these processes malfunction illnesses can result, such as osteoporosis.) These processes necessarily involve the circulation of calcium and phosphate within the body, and these ions are present in the body fluid which circulates among cells. Scientists already understand a lot about bone growth. During bone growth, calcium and phosphate ions from the body fluid are deposited at a site where new bone is required. These ions precipitate to form a solid calcium phosphate compound. Interestingly, the first compound formed is not the bone mineral hydroxyapatite. Hydroxyapatite is formed by subsequent reactions from the first compound.Surprisingly, the structure of the first calcium phosphate compound formed is still unknown, over 50 years after it was discovered. It was given the name amorphous calcium phosphate because it is not crystalline (amorphous means non-crystalline). Since it is not crystalline, it's structure cannot be identified using standard methods such as crystallography. Without knowing the structure of this compound, scientists are unable to describe the very early stage of bone formation, and hence a key piece of knowledge is missing.This proposal will provide the missing knowledge by applying special techniques to identify the structure of amorphous calcium phosphate. These techniques are ones which scientists have developed to study glasses, such as window glass, which are also non-crystalline. The techniques include special diffraction experiments (similar to crystallography) and computer modelling. These techniques have successfully revealed the structure of glasses, but they are less often applied to amorphous materials in biology.Knowing the structure of amorphous calcium phosphate will improve our knowledge of bone growth. This will provide important benefits. Firstly, for our understanding of biology (including illnesses such as urinary stones). Secondly, for scientists who are making bioactive materials, which are designed to be implanted in the body and to mimic the body's own bone growth processes. Thirdly, for scientists who want to find alternative ways to make minerals (without using geological processes).