Molecule-Guided Investigations into p53 Biology

伯纳尔实验室于2010年5月开始组建。在过去的几个月里，我们一直在致力于实验室的基础设施建设。现在，实验室空间的翻新和建造已经完成，大部分设备已经安装完毕，我们准备开始上面概述的调查。这个项目的工作是多学科的，它包括合成化学、生物化学、分子生物学和细胞生物学。随着最近在我的实验室安装了一个多肽合成器和一个液质联用(LC/MS)系统，我们准备设计、合成和提纯我们将在生物学研究中使用的装订多肽。我们目前的目标是构建包括SAH-P53小鼠变体(见目标部分)的化合物，泛素化相关蛋白质中环域相互作用的调节剂，以及阻断核受体激活功能和共激活物结合部位的多肽。在生物学方面，我们将处于有利地位，可以在内部研究我们将在实验室合成的所有分子。我们将探索化合物的生化和生物物理性质，并测试它们在蛋白质结合分析中的行为。它们的活性将使用重组蛋白和广泛的癌细胞株进行评估。

The setup of the Bernal Laboratory began in May of 2010. Over the course of the last few months, we have been dedicating our time to build the infrastructure of the laboratory. Now that the renovations and construction of the lab space has been completed and most of the equipment has been installed, we are poised to embark in the investigations outlined above. The work in this project is multi-disciplinary, and it comprises a mixture of synthetic chemistry, biochemistry, molecular biology and cell biology. With the recent installation of a peptide synthesizer and a liquid chromatography mass spectrometry (LC/MS) system in my laboratory, we are prepared to design, synthesize and purify the stapled peptides that we will use in our biological studies. We currently aim to construct compounds that include the murine variants of SAH-p53 (see Goals section), modulators of RING domain interactions in proteins involved in ubiquitylation, and peptides that block the activation function and coactivator binding site of nuclear receptors. On the biology front, we will be well-positioned to study in-house all of the molecules that we will synthesize in the laboratory. We will explore the biochemical and biophysical properties of the compounds and test their behavior in protein binding assays. Their activity will be assessed using both recombinant proteins and a wide array of cancer cell lines.