施一公的研究领域是结构生物学，他长期从事于细胞凋亡的分子机制、重要膜蛋白以及细胞内生物大分子机器的结构与功能研究。其在细胞凋亡研究领域，系统阐述了凋亡蛋白酶活性调控的分子机理，这与癌症的发生和治疗密切相关。关于谷氨酰胺和癌症，施一公曾在一次演讲中提到，他的团队通过研究发现，癌细胞很喜欢谷氨酰胺，喜欢的应该是里边的氨根离子，用氨根离子来抗酸。于是施一公吩咐他的学生，去给癌细胞脱氨，看看是不是可以有效抑制癌细胞的增生。果然不出他所料，通过脱氨可以有效抗癌。
此外，施一公教授的研究组近年来一直致力于病原微生物及癌细胞抗酸系统膜转运蛋白的研究，发表了一系列高影响力的科学论文。他们曾通过大量系统的生化分析首次发现并证实了决定抗酸系统3的膜转运蛋白AdiC的pH感受器，即其启动“开关”——蛋白上的第74位酪氨酸。在将此氨基酸“移除”的突变体上，AdiC蛋白的转运不再受到环境酸碱度的影响，在一定酸碱度范围内处于始终有活性的状态。进一步，研究者揭示了第74位酪氨酸如何控制蛋白感受酸碱度变化并调节活性的分子机理，通过氨基酸残基替换的比较研究，证实了这一过程是通过正电荷-π键相互作用来实现的，这种非常规氢键的键合作用是首次在蛋白感受外界环境酸碱度的过程中被发现。
The relationship between glutamine and cancer. What research has Shi Yigong conducted in this regard?
Shi Yigong's research field is structural biology. He has long been engaged in the research of the molecular mechanism of apoptosis, important membrane proteins, and the structure and function of intracellular biological macromolecular machines. In the field of apoptosis research, he systematically expounded the molecular mechanism of regulating the activity of apoptotic proteases, which is closely related to the occurrence and treatment of cancer. Regarding glutamine and cancer, Shi Yigong mentioned in a speech that his team found through research that cancer cells like glutamine very much. What they should like is the ammonium ion inside. They use ammonium ions to resist acid. So Shi Yigong instructed his students to remove the ammonia from cancer cells to see if it could effectively inhibit the proliferation of cancer cells. As expected, through deamination, it can effectively fight cancer.
In addition, Professor Shi Yigong's research group has been committed to the research of membrane transporter proteins of acid resistance systems in pathogenic microorganisms and cancer cells in recent years and has published a series of highly influential scientific papers. Through a large number of systematic biochemical analyses, they have for the first time discovered and confirmed the pH sensor of the membrane transporter protein AdiC that determines the acid resistance system 3, that is, its "switch" - tyrosine at position 74 on the protein. On the mutant with this amino acid "removed", the transport of the AdiC protein is no longer affected by the pH of the environment and is always active within a certain pH range. Further, the researchers revealed the molecular mechanism by which tyrosine at position 74 controls the protein's perception of pH changes and regulates its activity. Through comparative studies of amino acid residue substitutions, it was confirmed that this process is achieved through a positive charge-π bond interaction. This unconventional hydrogen bond bonding effect was discovered for the first time in the process of proteins sensing the pH of the external environment.
