Overseas Short Visit - Neutron Scattering Studies on DNA Compaction by Dendrimers

我们的目标是研究人造树突状分子对DNA的压实作用，作为了解像DNA这样的大分子如何被压缩到细胞核的小空间的项目的一部分。我们的总体目标（作为更大项目的一部分）是构建一个具有转录能力的真实细胞核的合成模拟物，以便创建一个合成蛋白质和其他治疗剂的系统。树状大分子是在这种合成的类似核中包装DNA的一种可能的方法。小角中子散射（SANS）技术使我们能够研究溶液中形成的纳米级结构，并利用结构中氢取代氘引起的广泛信号变化。这使我们能够在不显著改变系统化学成分的情况下显著增强信号，并为我们提供更多有关感兴趣结构的信息。超小角度散射（USANS）使用相同的技术来增强信号，并且可以测量比SANS大得多的结构，因此需要研究这种系统，其结构范围可以从小的单个树突- dna复合物到多个树突- dna聚集体。USANS目前还不能在英国使用，所以实验将在美国的NIST中子研究中心进行。这项工作是来自英国的一个小组和来自隆德的一个小组之间的合作，将有助于形成这些小组之间目前正在发展的持续合作的基础。申请人在溶液中聚合体的SANS测量方面具有丰富的经验，这是本实验所需要的，以便在实验期间现场做出影响收集数据的关键决策。这将确保我们最大限度地利用这些仪器上非常有限的实验时间。

We aim to study the compaction of DNA by artificial dendrimers as part of a project to understand how such large molecules as DNA can be compressed into the small space of a cell nucleus. Our overall goal (as part of a larger project) is to build a synthetic analogue of a real cell nucleus which is transcriptionally competent in order to create a system for synthesising proteins and other therapeutic agents. Dendrimers are one possible method towards packaging DNA in this synthetic analogue nucleus. Small angle neutron scattering (SANS) techniques allow us to study the nanoscale structures formed in solution and to take advantage of the wide variation in signal caused by substituting hydrogen in the structures for deuterium. This enables us to dramatically enhance the signal without significantly altering the chemistry of the system and gives us much more information about the structures of interest. Ultra-small angle scattering (USANS) uses the same technique to enhance the signal and can measure much larger structures than SANS, so is required to study this system where structures can range from small single dendrimer-DNA complexes up to multiple dendrimer-DNA aggregates. USANS is not currently available in the UK so the experiment will be carried out at the NIST Centre for Neutron Research in the US. The work is a collaboration between a group from the UK and one from Lund, and will help form the basis of an ongoing collaboration which is currently developing between these groups. The applicant has extensive experience in SANS measurements on aggregates in solution which will be required in this experiment so that critical decisions affecting the data to be collected can be made on the spot during the experiment. This will ensure that we make maximum use of the very limited experimental time available on these instruments.