招聘簡介：

　　美國國立衛(wèi)生研究院資助的博士后職位可在哈佛醫(yī)學(xué)院/馬薩諸塞州眼耳醫(yī)院的鄭一辰博士的實驗室中獲得，研究CRISPR/CAS9介導(dǎo)基因編輯治療遺傳性耳聾的開發(fā)和應(yīng)用。

　　我們有興趣將CRISPR/CAS9介導(dǎo)的基因組開發(fā)成新的基因治療范式，用于從動物模型到人類患者的遺傳性聽力損失。我們是第一個展示Crispr編輯劑（以RNP的形式存在的CAS9蛋白和SGRNA，核糖核酸蛋白）能有效地傳遞到哺乳動物毛細胞中，從而產(chǎn)生高效編輯（Nat Biotech）。zuris等人，2014年）。我們已經(jīng)證明，RNP提供編輯代理挽救了人類顯性耳聾小鼠模型的聽力（Nature，Gao等人，2018）。我們的主要目標(biāo)是開發(fā)針對聽力損失的基因組編輯療法，特別關(guān)注以下領(lǐng)域：1）。發(fā)展編輯技術(shù)，提高編輯效率和編輯專一性；開發(fā)新的運載工具，包括納米脂質(zhì)體，用于RNP運載編輯機械，以針對不同的體細胞；就地檢測編輯事件；4）。內(nèi)切酶生物工程提高活性；利用人類患者的iPS細胞改進CRISPR以糾正疾病表型；在大型動物模型（包括豬和7）中實現(xiàn)高效、準(zhǔn)確的編輯。開發(fā)新的編輯工具，針對同一耳聾基因的不同突變。

　　英文原文：

　　NIH funded postdoctoral positions are available in the laboratory of Dr. Zheng-Yi Chen of Harvard Medical School/Massachusetts Eye & Ear Infirmary on the development and application of CRISPR/Cas9-mediated gene editing to treat genetic deafness.

　　We are interested in developing CRISPR/Cas9-mediated genome into new gene therapy paradigm for genetic hearing loss from animal models to human patients. We are the first to show CRISPR editing agents (Cas9 protein and sgRNAs in the form of RNP, ribonucleotide proteins) can be efficiently delivered into mammalian hair cells resulting in high efficiency editing (Nat Biotech. Zuris et al2014). We have demonstrated that RNP delivery of editing agents rescued hearing in a mouse model of human dominant deafness (Nature, Gao et al., 2018). Our main focus is to develop genome editing therapy for hearing loss with particular interests in the following areas: 1). Development of editing technology to improve editing efficiency and specificity in vivo; 2). Developing new delivery vehicles including nanoparticle based liposomes for RNP delivery of editing machinery to target diverse somatic cells; 3). Detection of editing events in situ; 4). Bioengineering of endonucleases to improve activity; 5). Advance CRISPR to correct disease phenotype using iPS cells from human patients; 6). Achieve efficient and accurate editing in large animal models including pig and 7). Develop new editing tools to target different mutations in the same deafness gene.

　　The positions offer unique and exciting opportunities to engaging in developing cutting-edge CRISPR technology for inner ear application with direct implication in humans. The fellows will have the opportunity to conduct the development of CRISPR technology for hearing rescue in animal models in Boston and conduct pig model study in China. The project involves collaboration with Dr. Qiaobing Xu of Tufts University and Dr. David Liu of Broad Institute. We provide an interdisciplinary and collaborative environment in all aspects of hearing research. A successful candidate (Ph.D, M.D/Ph.D or MD) should have a strong background in genome editing technology, genetics, molecular biology and strong interest in application of editing technology to treat human diseases.

　　Please email a curriculum vita, a description of research accomplishments and names of three references to:

　　Zheng-Yi Chen, D.Phil. (617-909-6090)

　　Associate Professor

　　Harvard Medical School

　　Massachusetts Eye & Ear Infirmary

　　Zheng-Yi_Chen@meei.harvard.edu

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