龋病是一种多因素疾病，甜味感知能力与饮食习惯是影响龋病风险的重要因素。甜味受体T1R2/T1R3二聚体功能可影响个体甜味感知能力及龋病风险，但对调控甜味受体功能的分子机制仍缺乏深入研究。可变剪接通过前体mRNA不同剪接方式来影响蛋白质结构与功能，是广泛存在的转录后调控方式。课题组前期研究发现甜味受体存在可变剪接，且能够负向调控甜味受体功能；因此假设甜味受体可变剪接能够精细调控自身功能，进而影响甜味感知与龋病风险。为验证此假说，本项目拟全面系统找寻甜味受体可变剪接，进一步深入发掘调控甜味受体可变剪接的关键剪接因子；利用味蕾细胞分离培养、钙离子成像等技术体外探究可变剪接对甜味受体功能的影响及作用机制；利用小鼠甜味感知评价模型及龋病模型，验证甜味受体可变剪接对甜味感知及龋病风险的影响与作用机制。本项目以甜味受体可变剪接为切入点，阐明调控个体甜味感知的分子生物学机制，利于实现龋病多因素综合管理。

Since dental caries is a multifactory disease, dietary habit, as an essential cariogenic factor, should be taken into account when evaluating individual caries risk. It has been reported the capacity variance in sweet taste perception was related with different caries status, while the mechanism underlie was yet unclear. Researchers claimed that function of T1R2/T1R3 heterodimer, the sweet taste receptor (STR) , could affect the sweet taste perception ability and sweet food intake, thus contributing to caries protection/risk. Therefore, delineating the specific mechanism underlie STR function regulation is of vital importance. Alternativa splicing refers to the process that selectively splices a set of sites in a pre-mRNA to form variable mature mRNAs, thereby producing proteins with different structures and functions. Previously, we’ve identified several STR alternative transcripts, functioned as negative regulators against STR function. However, several questions need to be addressed, regarding the potential existence of other STR alternative transcrips, the way these alternative transcrips regulated, and whether STR alternative splicing could eventually affect sweet taste percetion. This proposal aimed to systemically identify alternative splicing events of STR, and also the key splicing fators responsible for the expression of certain alternative transcripts. Via taste bud cells isolation/culturing and calcium imaging assay, the impact of alternative splicing on STR function will be assessed. In addition, specific animal models will be utilized to evaluate the relationship between STR alternative splicing and sweet taste perception, as well as caries protection/risk. Results obtained from this proposed study illuminate molecular mechanisms by which STR function and sweet taste perception are modulated, and provide novel targets for comprehensive caries management.