Accelerating plant breeding by modulating recombination.

通过调节重组加速植物育种。

• 批准号: MR/T043253/1
• 负责人: Andrew Lloyd
• 金额: $ 158.92万
• 依托单位: Aberystwyth University
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT043253%2F1
• 关键词: Accelerating; plant; breeding; modulating; recombination.

To meet expected demand, the world will need to produce 50 percent more food in 2050 than it did in 2012. While similar growth rates have been achieved in the past, future growth faces the additional pressure of climate change and the need for reduced chemical inputs. Sustainably enhancing agricultural production is therefore a major challenge facing the sector.A valuable source of traits for disease resistance and abiotic stress tolerance resides in thousands of living wild crop relatives. Accessing these traits for plant breeding, however, is limited by "genetic drag", where low levels of genetic exchange (recombination) means that both desirable and undesirable "wild traits" are introduced and can be difficult to separate. Boosting recombination overcomes genetic drag allowing access to diverse germplasm, as well as increasing the efficiency of traditional breeding programs, helping generate the new combinations of traits required for crop improvement in fewer generations.Recombination can be increased in plants 8-fold by knocking out anti-recombinase genes. However, establishing multigene knockouts in every breeding program is not practical, approaches used to generate mutants may preclude cultivation in tightly (GMO) regulated environments and the mutations introduced can reduce fertility, so wild type alleles must be restored prior to cultivation. Transiently increasing recombination without modification of the recombination machinery itself would solve these problems.To achieve this goal, we will use high-throughput screening assays to identify small molecule inhibitors of key recombination suppressing proteins that can be used to transiently boost recombination in a wide variety of crop species. To identify inhibitors, we will design targeted compound libraries for screening based on molecules identified in large biomedical drug screens that inhibit human orthologs of our target proteins. In addition, virtual screening of large compound libraries will be used to identify further compounds of interest for testing. We will also identify and/or develop plant versions of peptides known to boost recombination in mammalian systems. Once identified, delivery of recombination boosting small-molecules will be optimised for use in crops. This will be initially be undertaken in Brassica and barley, covering a dicot crop closely related to the model plant Arabidopsis, and a key grain crop, both with well-developed cytological tools. Another route for crop development is to incorporate the traits and diversity of two genomes into a single individual - known as allopolyploidy. Allopolyploid plants are common in agriculture (e.g. wheat and cotton) as their fixed hybrid nature usually results in improved agricultural traits. Despite their potential, previous attempts to generate new allopolyploid crops have failed as they tend to have genomic instability and low fertility due to recombination between the two sub-genomes. Two interacting genes have recently been implicated in suppressing this inter-genomic recombination and we will assess the potential to use/modify these genes, and others in the same pathway, to engineer a stable meiosis in new allopolyploids. If successful we will use this approach to generate new genetically stable allopolyploid Brassica and pasture grasses.This multi-disciplinary project, draws on expertise of the Fellow and Project Partners in molecular plant science, phenomics, plant breeding, polyploidy, medicinal chemistry and biochemistry to modify recombination in plants for accelerated plant breeding, helping to develop the high nutrition, climate ready and disease resistant crops needed to meet future food needs. The final three years of the project will involve product development in collaboration with breeding companies to optimise delivery and effectiveness during plant breeding and establishment of a start-up company to commercialise the product(s) developed.

为了满足预期的需求，全世界在2050年的食物中需要比2012年的食物多50％。尽管过去已经达到了相似的增长率，但未来的增长面临着气候变化的额外压力以及化学输入减少的需求。因此，可持续增强的农业生产是该行业面临的主要挑战。疾病抵抗和非生物胁迫耐受性的宝贵特征属于成千上万的野生作物亲戚。然而，获得这些特征的植物育种受到“遗传阻力”的限制，在这种特征中，遗传交换的水平低（重组）意味着引入了理想和不希望的“野生特征”，并且很难分离。促进重组克服了遗传阻力，从而可以进入多种种质，并提高传统育种计划的效率，从而帮助产生更少世代的作物改善所需的新特征组合。在植物中可以增加抗抗组织酶基因的植物中的重组。但是，在每个繁殖计划中建立多基因敲除不实用，用于产生突变体的方法可能会在严格的（GMO）受调节的环境中排除培养，并且引入的突变可以降低生育能力，因此必须在培养之前恢复野生型等位基因。在不修改重组机制本身的情况下，瞬时增加重组将解决这些问题。为了实现这一目标，我们将使用高通量筛选测定法确定关键重组抑制蛋白的小分子抑制剂，这些抑制蛋白质可用于在多种农作物中迅速增强重组。为了鉴定抑制剂，我们将根据在大型生物医学药物筛选中鉴定的分子设计有针对性的化合物文库，以抑制我们靶蛋白的人类直系同源物。此外，将使用大型化合物库的虚拟筛选来识别进一步的测试感兴趣的化合物。我们还将确定和/或开发已知的肽的植物版本，以增强哺乳动物系统中的重组。一旦确定，重组促进小分子的递送将被优化用于农作物。最初，这将在Brassica和Barley进行，涵盖了与模型植物拟南芥密切相关的DICOT作物，以及具有良好发达的细胞学工具的关键谷物作物。农作物发育的另一种途径是将两个基因组的特征和多样性融入一个单个个体（称为杂质素）中。同种多倍体植物在农业（例如小麦和棉花）中很常见，因为它们的固定杂交性质通常会改善农业特征。尽管它们具有潜力，但以前的产生新的同多倍体作物的尝试却失败了，因为它们往往由于两个亚基因组之间的重组而具有基因组不稳定性和低生育能力。最近，两个相互作用的基因涉及抑制这种基因组间重组，我们将评估使用/修改这些基因的潜力，而在同一途径中使用了这些基因，以在新的同种倍倍体中设计稳定的减数分裂。 If successful we will use this approach to generate new genetically stable allopolyploid Brassica and pasture grasses.This multi-disciplinary project, draws on expertise of the Fellow and Project Partners in molecular plant science, phenomics, plant breeding, polyploidy, medicinal chemistry and biochemistry to modify recombination in plants for accelerated plant breeding, helping to develop the high nutrition, climate ready and disease resistant crops needed满足未来的食物需求。该项目的最后三年将涉及与育种公司合作的产品开发，以优化植物育种和成立初创公司，以商业化开发产品。

项目成果

Crossover interference: Just ZYP it.

交叉干扰：只需 ZYP 即可。

• DOI: 10.1073/pnas.2103433118
• 发表时间: 2021
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Crismani W

Meiosis in allopolyploid Arabidopsis suecica.

• DOI: 10.1111/tpj.15879
• 发表时间: 2022-08
• 期刊: PLANT JOURNAL
• 影响因子: 7.2
• 作者: Nibau, Candida;Gonzalo, Adrian;Evans, Aled;Sweet-Jones, William;Phillips, Dylan;Lloyd, Andrew
• 通讯作者: Lloyd, Andrew

Crossover patterning in plants.

• DOI: 10.1007/s00497-022-00445-4
• 发表时间: 2023-03
• 期刊: Plant reproduction
• 影响因子: 3.4