CAREER: Mechanisms and tradeoffs of dietary specialization in mammalian herbivores

在加工植物毒素的解毒系统的局限性被牵连的机制解释哺乳动物食草动物之间的饮食专业化的缺乏。事实上，人们对野生食草动物如何代谢植物毒素以及解毒如何限制饮食专业化知之甚少。由于大气中二氧化碳含量的上升，许多植物的毒素浓度在下一个世纪内将翻一番，因此，目前对去腐作用的限制很感兴趣。这项研究的首要目标是了解与食草林鼠（Neotoma）饮食专业化相关的机制。与通才相比，专家林鼠预计吸收较低浓度的植物毒素。该研究检查了可能减少毒素吸收的3种机制：1）单宁结合蛋白，2）p-糖蛋白和3）肠道解毒。专家和通才将进行比较，以确定他们在这些机制方面有何不同。将采用生物化学和药理学方法。 此外，理论预测，与处理相同化合物的通才食草动物相比，专家的解毒系统在处理饮食中的植物毒素方面更有效。 然而，专家在处理来自其饮食的毒素方面具有的上级能力预计会损害其生物转化新毒素的效率，这些毒素不包含在其正常饮食中。饮食专业化的潜在权衡将通过比较1）专家和通才可以摄入的新毒素的最大水平; 2）使用探针药物的解毒途径（功能化和葡萄糖醛酸化）的能力;和3）用DNA微阵列调查通才和专家的解毒系统来解决。 关于教育部分，建议为中级学生（初级-初级）开设一门强化课程，以本研究项目为范例和机会，对他们进行各方面的研究培训。 这门课程，“科学沉浸”，将在每年秋季学期提供给最多五名学生。

Limitations of the detoxification system in processing plant toxins are implicated as the mechanism explaining the paucity of dietary specialization among mammalian herbivores. In fact, little is known about how wild herbivores metabolize plant toxins and how detoxification restricts dietary specialization. Detoxification constraints are of current interest given that the toxin concentrations of many plants will double within the next century due to rising atmospheric CO2 levels. The overarching goals of the research are to understand the mechanisms that permit and tradeoffs associated with dietary specialization in herbivorous woodrats (Neotoma). Specialist woodrats are predicted to absorb lower concentrations of plant toxins compared to generalists. The research examines 3 mechanisms that may decrease toxin absorption: 1) tannin-binding proteins 2) p-glycoproteins and 3) intestinal detoxification. Specialists and generalists will be compared to determine how they differ with respect to these mechanisms. Biochemical and pharmacological methods will be employed. In addition, theory predicts that specialists have detoxification systems that are more efficient in processing plant toxins in their diet compared to generalist herbivores processing the same compounds. However, the superior ability that specialists have in processing toxins from their diet is predicted to compromise their efficiency to biotransform novel toxins, which are not contained in their normal diet. The potential tradeoffs of dietary specialization will be addressed by comparing 1) maximal levels of novel toxins that specialists and generalists can ingest; 2) capacities of detoxification pathways (functionalization and glucuronidation) using probe drugs; and 3) surveying the detoxification systems of generalists and specialists with DNA microarrays. For the education component, an intensive course is proposed for mid-level students (sophomore-junior) to train them in various aspects of research by using this research project as the example and opportunity. This course, "Scientific Immersion", will be offered in the fall semester each year to a maximum of five students.