CAREER: Mechanisms and tradeoffs of dietary specialization in mammalian herbivores

解毒系统在处理植物毒素方面的局限性被认为是解释食草哺乳动物缺乏饮食专门化的机制。事实上，我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浓度的上升，许多植物的毒素浓度将在下个世纪翻一番，因此解毒限制是当前的兴趣所在。该研究的首要目标是了解草食性木鼠饮食专业化的机制和权衡。据预测，与通才相比，专业木鼠吸收的植物毒素浓度较低。该研究探讨了3种可能减少毒素吸收的机制：1)单宁结合蛋白；2)p糖蛋白；3)肠道解毒。将对专家和通才进行比较，以确定他们在这些机制方面的差异。将采用生化和药理学方法。此外，理论预测，与处理相同化合物的通才食草动物相比，专业动物在处理饮食中的植物毒素方面具有更有效的排毒系统。然而，专家在处理他们饮食中的毒素方面的卓越能力预计会损害他们生物转化新毒素的效率，这些毒素不包含在他们的正常饮食中。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来解决；2)探针药物解毒途径（功能化和糖醛酸化）的能力；3)利用DNA微阵列研究多面手和专家的解毒系统。在教育方面，我们建议为中级学生（二、三年级）开设一门强化课程，以本研究项目为例和机会，训练他们在研究的各个方面。这门名为“科学沉浸”的课程将在每年秋季学期开设，最多招收5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.