Characterisation of a new mechanism of regulation for HIF1 and the hypoxic response.

我相信我们与BBSRC的记录和我们的出版物表明，我们可以实现这个令人兴奋的项目的目标，并成功地返回这个赠款与新的和重大的见解和进展LIMD1生物学和HIF信号通路。最佳水平的氧气需要在整个细胞和组织的我们的身体生存。被称为“氧稳态”，这在动物和实际上所有多细胞生物中受到严格调节，以确保组织充分供应氧气。虽然氧气水平在人体内的范围从上呼吸道中的21%到大多数器官中的平均5%，但每种组织类型都需要一定浓度的氧气，低于该浓度，基本的细胞过程如能量产生，蛋白质合成和细胞生长和分裂就会受损。细胞或组织对低氧浓度（“缺氧”）的快速反应和适应可以使细胞保持活力，从而减少对生物体的潜在损害。这被称为“缺氧反应”。缺氧反应的失调是癌症发展的一个关键特征，也是大肿瘤生长及其在全身扩散的一个关键特征。此外，这一关键细胞控制过程的失调也与许多非癌性疾病有关，如神经系统疾病、心肌梗死（心脏病发作）、中风和许多缺血性（低氧）相关疾病。因此，对这一关键细胞控制过程的分子生物学的完整理解仍然是全球基础细胞和分子生物学研究的重要焦点。为此，我们最近发现了一种名为LIMD1的蛋白质，它对调节缺氧反应的正常功能至关重要。此外，我们已经证明，这种蛋白质的丢失在细胞内产生了一个假缺氧环境，导致它的反应就像它处于上述缺氧疾病状态之一一样。因此，我们的发现代表了一个新的未知水平的分子生物学的缺氧反应的关键。此外，我们目前是世界上唯一一个研究低氧调节这一特定领域的小组，希望通过BBSRC奖，我们可以继续研究这一令人兴奋的新分子生物学。此外，这些信息将代表一个主要的新途径的调查基础和临床分子生物学研究人员在这一领域，并代表一组新的蛋白质靶点，为未来的发展缺氧疾病相关的药物疗法和治疗。

I believe our track record with the BBSRC and our publications demonstrate we can achieve the goals of this exciting project and successfully return this grant with novel and significant insights and advances to LIMD1 biology and the HIF signalling pathway.Optimum levels of oxygen are required throughout the cells and tissues of our body for survival. Referred to as 'oxygen homeostasis', this is tightly regulated in animals and indeed all multicellular organisms to ensure that tissues are sufficiently supplied with oxygen. Whilst oxygen levels range within the human body from 21% in the upper airway to an average of 5% in most organs, each tissue type has a requirement for a certain concentration of oxygen, below which essential cellular processes such as energy production, protein synthesis and cell growth and division become impaired. Rapid reaction and adaptation of a cell or tissue to low oxygen concentrations ('hypoxia') can enable cells to remain viable, thus reducing potential damage to the organism. This is known as the 'hypoxic response'. Deregulation of the hypoxic response is a key characteristic in cancer development and also large tumour growth and its spread throughout the body. Furthermore, deregulation of this key cellular control process is also linked to many non-cancerous diseases such as neurological disease, myocardial infarction (heart attacks), stokes, and many ischemic (low oxygen) related diseases. Therefore, a complete understanding of the molecular biology of this critical cellular control process remains an important focus for basic cell and molecular biology research worldwide. To this end we have recently identified a protein called LIMD1 that is a critical to regulating the normal function of the hypoxic response. Furthermore, we have shown that loss of this protein creates a pseudo-hypoxic environment within the cell, causing it to react as if it is in one of the hypoxic diseased states mentioned above. Our discovery therefore represents a new unknown level of molecular biology critical for the hypoxic response. Moreover, we are currently the only group in the world to be researching this specific area of hypoxic regulation, and hopefully with this BBSRC award, we can continue to investigate this exciting new molecular biology. Furthermore, such information will represent a major new avenue of investigation to basic and clinical molecular biological researchers in this field and represent a new set of protein targets for future development of hypoxic disease-related drug therapies and treatments.