Accelerating plant breeding by modulating recombination.

为了满足预期的需求，2050年世界需要比2012年多生产50%的粮食。虽然过去也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，并需要减少化学品投入。因此，可持续地提高农业产量是该部门面临的一项重大挑战。抗病性和非生物胁迫耐受性性状的宝贵来源存在于成千上万的野生作物亲戚中。然而，将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）意味着引入了期望的和不期望的“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，并提高传统育种计划的效率，有助于在更少的世代中产生作物改良所需的新性状组合。通过敲除抗重组酶基因，植物中的转化率可以提高8倍。然而，在每个育种计划中建立多基因敲除是不切实际的，用于产生突变体的方法可能会妨碍在严格（GMO）调控的环境中培养，并且引入的突变会降低生育力，因此必须在培养之前恢复野生型等位基因。暂时增加重组而不修改重组机制本身将解决这些问题。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，这些蛋白可用于暂时促进各种作物物种的重组。为了鉴定抑制剂，我们将设计靶向化合物库，以基于在大型生物医学药物筛选中鉴定的分子进行筛选，这些分子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鉴定更多感兴趣的化合物以进行测试。我们还将鉴定和/或开发已知在哺乳动物系统中促进重组的肽的植物版本。一旦确定，重组促进小分子的递送将被优化用于作物。这将首先在芸苔属和大麦中进行，涵盖与模式植物拟南芥密切相关的双子叶植物作物，以及一种关键的谷物作物，两者都具有发达的细胞学工具。作物发展的另一条途径是将两个基因组的性状和多样性整合到一个个体中-称为异源多倍体。异源多倍体植物在农业中是常见的（例如小麦和棉花），因为它们的固定杂交性质通常导致改善的农业性状。尽管它们具有潜力，但先前产生新的异源多倍体作物的尝试失败了，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力。两个相互作用的基因最近被牵连在抑制这种基因组间重组，我们将评估潜在的使用/修改这些基因，和其他在同一途径，工程师在新的异源多倍体稳定减数分裂。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属和牧草。这个多学科的项目，借鉴了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的专业知识，以修改植物重组，加速植物育种，帮助开发高营养，气候适应和抗病作物需要满足未来的粮食需求。该项目的最后三年将涉及与育种公司合作进行产品开发，以优化植物育种过程中的交付和有效性，并建立一家初创公司，将开发的产品商业化。

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.