News.hust.edu.cn (Correspondent Liu Na), October 14 - Nature Communications online published a research paper of Associate Professor Xiao Xianjin of the Institute of Reproductive Health entitled Thermodynamics and kinetics guided probe design for uniformly sensitive and specific DNA hybridization without optimization.

Sensitive and specific DNA hybridization is essential and fundamental for nucleic acid chemistry. Competitive composition of probe and blocker has been the most adopted probe design for its relatively high sensitivity and specificity. However, there exists an intrinsic inverse correlation between sensitivity and specificity of the competitive probe system, which led to labour-intensive optimization of the sequence design and reaction conditions to achieve a balanced performance. Thus, high-throughput analysis of multiple mutations, which required design of multiple compositions of blockers and probes, was very difficult and time-consuming.

The research group led by Xiao Xianjin has built a theoretic model of competitive DNA hybridization and deeply revealed the fundamental originof the inverse correlationbetween the sensitivity and specificity from the perspectives of thermodynamics and kinetics. To solve the bottleneck problem, the research group has invented the 4-way Strand Exchange LEd Competitive DNA Testing system (4-way SELECT system), which broke the essential contradiction between the sensitivity and the specificity, realized the test of the 16 hot-potmutations of the human genomes without optimization, and verified the clinical utility of the method in the actual samples of ovarian cancer. Our work brought up a new perspective and represented a novel category of detection in the field of nucleic acid probes. The reviewers of Nature Communications have highly evaluated it and they have unanimously regarded it as an important contribution to the field

Figure (a) 4-way SELECT System Reaction Mechanism and the Corresponding Free Energy Change. Figure (b) and Figure (c) Changes of the Sensitivity (Figure b) and Specificity (Figure c) of the 4-way SELECT System Varying with the Competitive Chain Concentration and Length Change. Figure (d) 2-dimensional Cross-interface Diagram of Figure b and Figure c with the Competitive Chain Length Being Fixed.

The research work has been greatly supported by the research group of Professor Zhao Meiping of the College of Chemistry and Molecular Engineering of Peking University and the research group ofProfessor Wang Hongbo of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Their collaboration reflected the advantages and great potential of interdisciplinary innovation. At present, Associate Professor Xiao Xianjin has been hired as an adjunct associate professor of the Union Hospital,Tongji Medical College, Huazhong University of Science and Technology. He will continue his interdisciplinary integration of the methodological research and the translational research of clinical medicine, and implement the development strategy raised by the university: “Interdisciplinary collaboration between clinical medicine and natural and applied science”.  

The Institute of Reproductive Health of Tongji Medical College is the first completion unit of the paper. Chen Xin, an eight-year clinical medicine undergraduate who entered the college in 2014, Liu Na, a master candidate of the Institute of Reproductive Health who entered the institute in 2017, and Liu Liquan, an eight-year clinical medicine undergraduate who entered the college in 2015, are the co-first authors. Associate Professor Xiao Xianjin of the Institute of Reproductive Health, Professor Zhao Meiping of Peking University and Professor Wang Hongbo of the Union Hospital are the co-corresponding authors of the paper.

Associate Professor Xiao Xianjin joinedthe Institute of Reproductive Health in 2016. At present, he has presided over eight projects such as the youth project and general project of the National Natural Science Foundation of China, and the important scientific and technological research topics of Hubei Province, and won some talent prizes such as the prize of Wuhan Youth Program and the New Academic Researcher Prize of Huazhong University of Science and Technology. Since he started to work in the institute three years ago, he has published one paper as a first author and 10 papers as the corresponding author, including Nature Communications (IF: 11.878) and Nucleic Acids Research (IF:11.147). The total impact factor has exceeded 70. In addition, Associate Professor Xiao Xianjin has actively explored the scientific research cultivation plan for the eight-year clinical medicine undergraduates. At present, the research group has admitted 10 eight-year clinical medicine undergraduates and published four first-author papers, and two of the eight-year undergraduates have respectively won the first prize and second prize of the Excellent University Student Scientific Research Award of Hubei Province.  

The Institute of Reproductive Health has vigorously supported interdisciplinary innovation and frontier exploration for a long time and provided good environment for the development of the young scholars. Meanwhile, the institute encourages the undergraduates to get to know reproductive medicine and participate in relevant scientific researches, and these endeavors have laid a solid foundation for the construction of an undergraduate program in reproductive medicine.

Link to the whole paper: https://www.nature.com/articles/s41467-019-12593-9