本科直博成功！癌症科学博士！-新东方前途出国

学生本科毕业后申请美国并不顺利，再加上疫情和其他因素所致，立刻把目标转向了医学方面同样优秀的英国大学。

曼彻斯特大学是世界前30的知名学府，历史悠久。 Dr A Latif,  Dr A Stevens,  Dr A Hurlstone三位教授所引领的PHD项目，与学生目标意愿十分贴合。我们定位好申请方案后，重新打造针对英国大学风格的个人文书材料，尽快为学生进行了套磁与申请。

不久后，项目老师们向同学抛来了面试的橄榄枝，经历了十余次的面试沟通，最终学校获得了2021年秋季入学的博士门票！

以下是此PHD项目的具体介绍：

Affiliations:Division of Infection, Immunity & Respiratory Medicine (L5)Division of Infection, Immunity & Respiratory MedicineLydia Becker Institute of Immunology and InflammationSchool of Biological Sciences

Monocarboxylate transporter 1 (MCT1) is a transmembrane protein involved in cell metabolism and mediates transport of monocarboxylates (such as pyruvate {a metabolic substrate} and lactate {a metabolic by product}) in and out of the cell. Increased plasma membrane (PM) expression of MCT1 has been reported in several cancer types including endometrial cancer (EC) and is associated with reduced patient survival. Although nucleus is not a usual location for MCTs (based on current knowledge on their function), we and others reported nuclear MCT1 (nMCT1) expression in endometrial [2] and soft sarcoma [3] biopsies. Both studies showed that patients with nMCT1 survive longer than the patients without it. Further, a number of studies showed that metabolic proteins found in the nucleus can regulate transcription and chromatin remodelling by acting as co-factors or by providing the substrates (such as lactate, acetyl-coA) for these processes (reviewed in [4, 5]). Interestingly, we also found that when in nucleus, MCT1 interacts with other proteins that modify chromatin remodelling and regulate gene expression. Therefore, understanding nMCT1’s novel role in nucleus is vital to identify and exploit novel approaches in cancer treatment to enhance life-expectancy amongst patients. This project aims to identify nMCT1s role in relation to potential chromatin remodelling and/or metabolomic changes involved in cancer progression and patient survival. For this purpose, we will first combine CRISPR-Cas9 technology with molecular cloning to engineer cancer cell lines (Ishikawa and HEC1A) with MCT1 protein targeted specifically to the nucleus (nMCT1) or plasma membrane (PM MCT1). We will then subject these cell lines to a number of in vitro methods (e.g. immunofluorescence, western blotting, electron microscopy) to characterise subcellular localisation and expression levels in engineered cell lines. Metabolic profile of the engineered cell lines with nMCT1 wand PM MCT1 will be performed using mass spectroscopy and data analysis will be performed using R package. Changes in chromatin remodelling will be assessed using ATAC-sequencing. Results of metabolomics and chromatin remodelling will be compared and correlated to evaluate correlation between MCT1 subcellular localisation, changes in metabolism and chromatin structure by using R or any other relevant bioinformatics tools. By the end of this interdisciplinary project, the selected student will be equipped in sought after wet lab and bioinformatics skills for post-doctoral positions.