12th International Workshop on Ataxia-Telangiectasia and ATM

描述（由申请人提供）：共济失调-毛细血管扩张症（a-t）是一种罕见的常染色体隐性遗传病，其发病率约为4万至10万分之一。A-T的特点是进行性小脑共济失调、毛细血管扩张、免疫缺陷、染色体不稳定、辐射敏感性和淋巴细胞恶性肿瘤发生率增加。A-T的症状通常表现在生命的最初几年，当儿童表现出步态不稳。神经肌肉控制的丧失是无情的，到十几岁的时候，孩子们通常只能坐在轮椅上。A-T患者通常在生命的第二个十年死于感染和/或淋巴瘤。此外，据估计，高达1%的普通人群携带ATM（共济失调-毛细血管扩张突变）基因的一个等位基因突变，而ATM杂合子患乳腺癌的风险增加。ATM基因编码一个大的（369 kDa）蛋白ATM，它是丝氨酸苏氨酸蛋白激酶（PIKKs）的磷脂酰肌醇3激酶家族的成员。缺乏ATM的细胞对电离辐射（IR）高度敏感，并且在响应IR和其他DNA损伤剂时激活多个细胞周期检查点存在缺陷。自1995年发现该基因以来，人们已经清楚地认识到，ATM在调节细胞对IR和其他DNA损伤因子的反应中起着关键作用。了解ATM的功能对于了解该疾病的病因、A-T患者和ATM杂合子增加癌症易感性的分子基础以及控制细胞对放疗和许多化疗药物反应的分子机制具有相当重要的意义。在此申请中，请为将于2006年9月8日至12日在加拿大阿尔伯塔省班夫班夫中心举行的第12届共济失调-毛细血管扩张和ATM国际研讨会提供部分资金支持。会议的目标：会议的目标是在非正式但刺激的科学氛围中，将基础和临床研究人员聚集在一起，研究A-T的临床特征、ATM在DNA损伤反应中的作用以及ATM在神经系统中的作用，这将促进科学互动、讨论和研究合作，以了解ATM的功能和A-T的生物学基础。我们的目标是促进研究，从而更好地理解和治疗甲氧腺苷t。特定区域集中的会议将包括ATM的作用和相关蛋白质的DNA损伤反应,激活的染色质ATM的重要性,ATM的作用在神经系统中,神经退化的机制,其他蛋白质DNA损伤神经病变的作用,动物模型t, ATM在乳腺癌和其他人类癌症流行病学的ATM基因突变,对t的新疗法的发展,和一个更新一个t的临床试验。

DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder that affects approximately 1 in 40,000 to 1 in 100,000 live births. A-T is characterized by progressive cerebellar ataxia, telangiectasia, immunodeficiency, chromosomal instability, radiation sensitivity and increased incidence of lymphoid malignancies. Symptoms of A-T usually manifest in the first few years of life when children exhibit wobbly gait. Loss of neuromuscular control is relentless and, by their teens, children are usually confined to a wheel chair. A-T patients usually succumb to infection and/or lymphoma in the second decade of life. In addition, it has been estimated that up to 1% of the general population carries mutations in one allele of the ATM (ataxia-telangiectasia mutated) gene and ATM heterozygotes have an increased risk of developing breast cancer. The ATM gene encodes a large (369 kDa) protein, ATM, that is a member of the phosphatidyl inositol 3 kinase family of serine threonine protein kinases (the PIKKs). Cells that lack ATM are highly sensitive to ionizing radiation (IR) and are defective in the activation of multiple cell cycle checkpoints in response to IR and other DNA damaging agents. Since the discovery of the gene in 1995, it has become apparent that ATM plays a critical role in regulating the cellular response to IR and other DNA damaging agents. Understanding the function of ATM is of considerable importance to understanding the etiology of the disease, the molecular basis for increased cancer predisposition in A-T patients and ATM heterozygotes, and the molecular mechanisms that control how cells respond to radiotherapy and many chemotherapeutic drugs. In this application, funds are requested for partial support towards the 12th International Workshop on Ataxia-Telangiectasia and ATM, which will be held at the Banff Centre, Banff, Alberta, Canada, September 8th to 12th 2006. Objectives of the meeting: The objectives of the meeting are to bring together basic and clinical researchers working on various aspects of the clinical features of A-T, the role of ATM in the DNA damage response, and the role of ATM in the nervous system, in an informal but stimulating scientific atmosphere which will promote scientific interactions, discussions and research collaborations into understanding the functions of ATM and the biological basis of A-T. Our goal is to stimulate research that will lead to better understanding of and treatments for A-T. Specific areas of focus of the meeting will include the role of ATM and related proteins in the DNA damage response, the importance of chromatin in the activation of ATM, the role of ATM in the nervous system, mechanisms of neurodegeneration, the role of other DNA damage proteins in neuropathies, animal models of A-T, ATM in breast and other human cancers, epidemiology of ATM mutations, towards the development of new treatments for A-T, and an update on clinical trials for A-T.