Integrated PhD Biomedical Science

在这个项目中，我们将评估化学修饰的核酸是否可以用于恢复OCA中的黑色素生成，从而可能逆转与该疾病相关的视力丧失。与作用于蛋白质的传统药物不同，核酸疗法靶向疾病的遗传蓝图，并正在成为一种强大的新型精准药物。我们将使用有机化学来设计和合成新的化学修饰，并评估这些修饰是否能增强核酸治疗剂的活性。我们将针对一种常见的致病性变异，Self小组已将其确定为OCA的重要贡献者。虽然该项目的重点是开发OCA的核酸疗法，但产生的化学修饰可能适用于许多其他疾病，包括罕见疾病和目前被认为是“坚不可摧”的疾病。这是一个跨学科项目，您将在学生期间接受一系列有机和化学生物学技术的培训。这些将包括合成有机化学，固相寡核苷酸化学，生物物理和生物化学技术，以及细胞培养中的生物测定。

In this project, we will evaluate whether chemically modified nucleic acids can be used to restore melanin production in OCA, potentially reversing sight loss associated with the disease. Unlike conventional drugs which act on proteins, nucleic acid therapeutics target the genetic blueprint of a disease and are emerging as a powerful new class of precision medicines. We will use organic chemistry to design and synthesise new chemical modifications and evaluate whether these enhance the activity of nucleic acid therapeutics. We will target a common pathogenic variant which the Self group have identified as a significant contributor to OCA. Whilst this project focuses on developing nucleic acid therapeutics for OCA, the chemical modifications generated are likely to be applicable to many other diseases, including rare and those currently considered 'undruggable'.This is an interdisciplinary project, and you will receive training in a range of organic and chemical biology techniques during the studentship. These will include synthetic organic chemistry, solid-phase oligonucleotide chemistry, biophysical and biochemical techniques, and biological assays in cell culture.