Characterization and function of a novel receptor in smooth muscle cells

被称为受体的蛋白质位于细胞表面。化合物与受体结合，引起细胞反应，调节组织和器官的正常功能。受体是多种多样的，其重要性随细胞类型的不同而不同。例如，在血管中，平滑肌细胞调节血液流动，在向器官输送氧气和营养物质方面起着重要作用。在血管中，平滑肌上的受体可以使它们缩短或收缩，从而增加血液流动的阻力。超过80%的药物以平滑肌细胞表面的受体为靶点。对于许多受体来说，激活受体的化学物质（配体）的身份是未知的。我们称后者为孤儿受体。确定孤儿受体的配体是制药行业开发新药实体的一种策略。因此，鉴定孤儿受体的配体可能是一项重大的科学发现，可以对研究界和社会产生长期影响。******我们NSERC研究的目标是研究一种新的受体，通过观察它如何引起血管收缩，从而改变整个生物体的血液流动。我们还将利用这些信息来查看受体是否在其他地方被发现，并确定其在其他组织和系统中的功能。******在之前发表的工作中，我们发现了一种在血管平滑肌细胞功能中起作用的新型受体。这种受体引起血管收缩，这将导致血压升高，减少流向器官的血液。这个程序的特别新颖之处在于，受体的身份和与配体（测试化合物）相关的生物活性范围尚未确定。******我们将利用从小鼠血管中分离的细胞进行实验室实验，以确定受体并描述导致平滑肌收缩的生化机制。为了证明我们的结果对整个生物体都有意义（生理上的重要性），我们将在活体动物身上进行试验，研究一种激活收缩机制的化合物。进一步的实验将首先用于进一步表征该受体在血管组织中的活性和功能；之后在其他组织中。******该计划将支持培养高素质的博士科学家，这些科学家将极有可能做出具有广泛科学影响的原创发现。这些人将具备技能，使他们能够高度适应未来不同的研究环境，无论是在学术界还是在行业研究中，并将拥有领导研究团队的经验。******该项目将建立关于细胞受体的实验室基础科学证据，可能会为未来的技术转让和商业化创造新材料。

Proteins called receptors are on the surfaces of cells. Chemical compounds bind to receptors and cause cell responses that regulate the normal function of tissues and organs. Receptors are diverse and their importance varies according to the type of cell. For example, in blood vessels the smooth muscle cells regulated blood flow, an important role in oxygen and nutrient delivery to organs. In blood vessel the receptors on smooth muscle can cause them to shorten or contract, which increases the resistance to blood flow. More than 80% of pharmaceutical drugs target receptors like those present on the surface of smooth muscle cells. For many receptors, the identity of the chemicals (ligands) that activate the receptor are unknown. We call these latter type orphan receptors. Identifying the ligands for orphan receptors is one strategy being used by the pharmaceutical industry to develop new drug entities. Therefore, identifying the ligands for an orphan receptor can be a significant scientific discovery that can have long-term impact on the research community and society.******The goal of our NSERC research is to study a novel receptor by looking at how it causes blood vessel contraction and thereby changes blood flow in whole organisms. We will also use this information to see whether the receptor is found elsewhere and to determine its function in those other tissues and systems.******In previously published work, we identified a novel receptor that has a role in vascular smooth muscle cell function. This receptor causes blood vessel constriction, which would be anticipated to increase blood pressure and decrease blood flow to organs. What is particularly novel about this program is that the identity of the receptor and the scope of biological activities associated with the ligand (test-compound) have not been determined.******We will conduct lab experiments to identify the receptor and describe the biochemical mechanisms that cause smooth muscles to contract by using cells isolated from blood vessels of mice. To show that our results have meaning for the whole organism (the physiological importance), we will conduct testing in live animals to study a compound that activates the contraction mechanism. Additional experiments will be used to further characterize the activity and function of this receptor in vascular tissues first; later in other tissues.******This program will support the training of highly-qualified PhD scientists that will be highly likely to make original discoveries with broad scientific impact. These people will have skills to make them highly adaptable to different future research environments either in academia or industry research and will have experience with leading research teams. ******This program will establish laboratory basic science evidence about a cell receptor that may lead to creation of new materials for future technology transfer and commercialization.