Unveiling the molecular basis of chromatinopathies to delineate innovative therapeutic solutions
揭示染色质病变的分子基础,描绘创新的治疗解决方案
基本信息
- 批准号:EP/X027007/1
- 负责人:
- 金额:$ 33.8万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2023
- 资助国家:英国
- 起止时间:2023 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Chromatinopathies (CPs) are a group of rare genetic diseases, which share clinical features as well as causal genetic alterations, leading to the inactivation of chromatin regulators involved in gene expression control and 3D chromatin organization. Within the framework of Chrom_Rare, we will focus on a group of clinically well-defined CPs, including Kabuki Syndrome, CHARGE Syndrome, Rubinstein-Taybi Syndrome and Cornelia de Lange Syndrome. Although the causative genes for these CPs have been identified, the consequences of their inactivation both at the molecular and functional level, have not been defined. The clinical features of CPs vary widely, suggesting that the impact of the haploinsufficiency of the affected chromatin regulators could depend on the epigenetic state and/or interactions with additional genetic and environmental factors. Hence understanding the genetic and epigenetic determinants of CPs represent an immediate medical need, as this will ultimately facilitate reaching the development of new therapeutic approaches. Our main goal is to set-up an intra-sectoral, cross-disciplinary training programme that would prepare the next generation of researchers equipped with advanced theoretical, technical and computational skills to study fundamental aspects of chromatin biology and their impact on CPs. In parallel, Chrom_Rare will devise new strategies to translate the molecular findings into new diagnostic and therapeutic approaches for patients affected by CPs. To enable understanding the molecular basis of chromatinopathies, we aim at developing multiple disease models recapitulating the main clinical features of CPs (WP1), investigating the genetic, epigenetic and topological determinants of CPs (WP2) and uncovering perturbed regulatory circuitries suitable for therapeutic intervention (WP3). Overall Chrom_rare will address unmet socio-economic, medical and scientific needs, for the understanding and possible treatment for CPs.
染色质病变(chroinopathies, CPs)是一组罕见的遗传性疾病,它们具有共同的临床特征和因果遗传改变,导致参与基因表达控制和三维染色质组织的染色质调节因子失活。在Chrom_Rare的框架内,我们将重点关注一组临床定义明确的CPs,包括Kabuki综合征、CHARGE综合征、Rubinstein-Taybi综合征和Cornelia de Lange综合征。虽然已经确定了这些CPs的致病基因,但它们在分子和功能水平上失活的后果尚未确定。CPs的临床特征差异很大,这表明受影响的染色质调节因子单倍体功能不全的影响可能取决于表观遗传状态和/或与其他遗传和环境因素的相互作用。因此,了解cp的遗传和表观遗传决定因素代表了迫切的医学需求,因为这将最终促进新治疗方法的发展。我们的主要目标是建立一个部门内、跨学科的培训计划,为下一代研究人员提供先进的理论、技术和计算技能,以研究染色质生物学的基本方面及其对cp的影响。同时,Chrom_Rare将设计新的策略,将分子发现转化为新的诊断和治疗方法,用于受CPs影响的患者。为了理解染色质病变的分子基础,我们旨在建立多种疾病模型,概括CPs (WP1)的主要临床特征,研究CPs (WP2)的遗传、表观遗传和拓扑决定因素,并揭示适合治疗干预的失调调节回路(WP3)。总体而言,Chrom_rare将解决尚未满足的社会经济、医疗和科学需求,以了解和可能治疗cp。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Siddharth Banka其他文献
Clinical, genetic, epidemiologic, evolutionary, and functional delineation of emTSPEAR/em-related autosomal recessive ectodermal dysplasia 14
emTSPEAR/em 相关常染色体隐性遗传性外胚层发育不良 14 的临床、遗传、流行病学、进化和功能描述
- DOI:
10.1016/j.xhgg.2023.100186 - 发表时间:
2023-04-13 - 期刊:
- 影响因子:3.600
- 作者:
Adam Jackson;Sheng-Jia Lin;Elizabeth A. Jones;Kate E. Chandler;David Orr;Celia Moss;Zahra Haider;Gavin Ryan;Simon Holden;Mike Harrison;Nigel Burrows;Wendy D. Jones;Mary Loveless;Cassidy Petree;Helen Stewart;Karen Low;Deirdre Donnelly;Simon Lovell;Konstantina Drosou;J.C. Ambrose;Siddharth Banka - 通讯作者:
Siddharth Banka
Trisomy 18 mosaicism: report of two cases
- DOI:
10.1007/s12519-011-0280-x - 发表时间:
2011-11-21 - 期刊:
- 影响因子:4.500
- 作者:
Siddharth Banka;Kay Metcalfe;Jill Clayton-Smith - 通讯作者:
Jill Clayton-Smith
Variants in emZFX/em are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt
emZFX/em 中的变体与一种具有反复性面部完形的 X 连锁神经发育障碍有关。
- DOI:
10.1016/j.ajhg.2024.01.007 - 发表时间:
2024-03-07 - 期刊:
- 影响因子:8.100
- 作者:
James L. Shepherdson;Katie Hutchison;Dilan Wellalage Don;George McGillivray;Tae-Ik Choi;Carolyn A. Allan;David J. Amor;Siddharth Banka;Donald G. Basel;Laura D. Buch;Deanna Alexis Carere;Renée Carroll;Jill Clayton-Smith;Ali Crawford;Morten Dunø;Laurence Faivre;Christopher P. Gilfillan;Nina B. Gold;Karen W. Gripp;Emma Hobson;Marwan Shinawi - 通讯作者:
Marwan Shinawi
Null and missense mutations of emERI1/em cause a recessive phenotypic dichotomy in humans
emERI1/em 的无义和错义突变在人类中导致隐性表型二分法
- DOI:
10.1016/j.ajhg.2023.06.001 - 发表时间:
2023-07-06 - 期刊:
- 影响因子:8.100
- 作者:
Long Guo;Smrithi Salian;Jing-yi Xue;Nicola Rath;Justine Rousseau;Hyunyun Kim;Sophie Ehresmann;Shahida Moosa;Norio Nakagawa;Hiroshi Kuroda;Jill Clayton-Smith;Juan Wang;Zheng Wang;Siddharth Banka;Adam Jackson;Yan-min Zhang;Zhen-jie Wei;Irina Hüning;Theresa Brunet;Hirofumi Ohashi;Philippe M. Campeau - 通讯作者:
Philippe M. Campeau
Pathogenic variants in emKMT2C/em result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes
emKMT2C/em 中的致病变体导致一种不同于 Kleefstra 和 Kabuki 综合征的神经发育障碍
- DOI:
10.1016/j.ajhg.2024.06.009 - 发表时间:
2024-08-08 - 期刊:
- 影响因子:8.100
- 作者:
Dmitrijs Rots;Sanaa Choufani;Victor Faundes;Alexander J.M. Dingemans;Shelagh Joss;Nicola Foulds;Elizabeth A. Jones;Sarah Stewart;Pradeep Vasudevan;Tabib Dabir;Soo-Mi Park;Rosalyn Jewell;Natasha Brown;Lynn Pais;Sébastien Jacquemont;Khadijé Jizi;Conny M.A. van Ravenswaaij-Arts;Hester Y. Kroes;Constance T.R. M. Stumpel;Charlotte W. Ockeloen;Siddharth Banka - 通讯作者:
Siddharth Banka
Siddharth Banka的其他文献
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