Accelerating plant breeding by modulating recombination.

为了满足预期的需求，到2050年，世界需要比2012年多生产50%的粮食。虽然过去已经实现了类似的增长率，但未来的增长将面临气候变化的额外压力和减少化学品投入的需要。因此，可持续地提高农业生产是该部门面临的一项重大挑战。抗病和抗非生物胁迫特性的宝贵来源存在于成千上万的野生作物近缘种中。然而，获得这些性状用于植物育种受到“遗传阻力”的限制，其中低水平的遗传交换（重组）意味着引入了理想和不理想的“野生性状”，并且可能难以分离。促进重组可以克服遗传阻力，从而获得多样化的种质资源，同时提高传统育种计划的效率，有助于在更少的世代内产生作物改良所需的新性状组合。敲除抗重组酶基因可使植物的重组增加8倍。然而，在每个育种计划中建立多基因敲除是不现实的，用于产生突变的方法可能会妨碍在严格（转基因）调控的环境中培养，并且引入的突变可能会降低生育力，因此必须在培养前恢复野生型等位基因。在不修改重组机制本身的情况下，瞬间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方法来鉴定关键重组抑制蛋白的小分子抑制剂，这些蛋白可用于短暂促进多种作物物种的重组。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抑制靶蛋白的人类同源物的分子设计靶向化合物文库进行筛选。此外，大型化合物库的虚拟筛选将用于确定进一步的感兴趣的化合物进行测试。我们还将鉴定和/或开发已知的促进哺乳动物系统重组的肽的植物版本。一旦确定，重组促进小分子的递送将优化用于农作物。这项工作将首先在芸苔属和大麦上进行，包括一种与模式植物拟南芥密切相关的双科作物，以及一种关键的粮食作物，两者都有发达的细胞学工具。作物发育的另一种途径是将两个基因组的特性和多样性整合到一个单独的个体中——称为异源多倍体。异源多倍体植物在农业中很常见（如小麦和棉花），因为它们的固定杂交性质通常会改善农业性状。尽管它们具有潜力，但由于两个亚基因组之间的重组，它们往往具有基因组不稳定性和低育性，因此以前尝试产生新的异源多倍体作物都失败了。两个相互作用的基因最近被认为与抑制这种基因组间重组有关，我们将评估使用/修改这些基因和其他基因的潜力，以在新的异源多倍体中设计稳定的减数分裂。如果成功，我们将利用这种方法产生新的遗传稳定的异源多倍体芸苔和牧草。这个多学科项目利用研究员和项目合作伙伴在分子植物科学、表型组学、植物育种、多倍体、药物化学和生物化学方面的专业知识，修改植物的重组，以加速植物育种，帮助开发高营养、耐气候和抗病的作物，以满足未来的粮食需求。项目的最后三年将涉及与育种公司合作开发产品，以优化植物育种期间的交付和有效性，并建立一家初创公司，将所开发的产品商业化。

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.