CAREER: Studying Weak Interactions in Biological Systems, Forming Strong Interactions Between Students

为了使信号分子在细胞内的传递发生，包裹信号分子的囊泡膜必须与另一膜融合。由于时间在细胞过程中至关重要，信号分子的传递必须准备好，只有当适当的信号或细胞信号组合发生时才会触发。虽然这是一个关键的细胞事件，但这种受调节的递送是如何发生的尚不清楚。膜是由各种各样的脂质组成的，它们之间的相互作用很弱，膜内的相互作用由脂质的化学结构和局部环境决定。这些因素决定了所得脂质的活性（有效浓度），从而决定了膜如何被蛋白质结合或分割。在该模型中，假设脂质之间的内在弱相互作用对于系统可逆和快速组织调节信号的蛋白质簇至关重要。这为生物事件提供了一种更细致的调节，而不是由少数非常强的相互作用所主导的系统。这些小的相互作用能量为脂质如何结合提供了灵活性，以响应蛋白质结合，形成信号平台。这个概念被假设为参与调节递送的关键蛋白如何靶向不同膜的基础。这个项目的目的是测试这样一个假设，即这些关键蛋白质不是由一些强相互作用调节的，而是由细胞膜上必要的弱相互作用的集合调节的。测试将涉及定量分析和严格使用结合理论和热力学（链接）关系的本科生来自不同的科学学科。这个项目还将产生概念和实验两方面的新技术，这些技术将适用于许多与生物学有关的问题。链接关系的经典应用是基于问题的学习的一个例子，其中生物过程被简单地以数学方式表示和解释。每个实验都成为一个案例研究，方程的推导不再局限于指定的家庭作业或经过多年的研究生训练后使用。目标是证明本科生和年轻的研究生可以提出、使用、探索和测试这些概念。更广泛的影响本项目的更广泛的影响包括开发方法，这些方法将增强女性在科学事业中的持久性、留任性和未来的成功。通过改善妇女的教育环境，不仅可以改善代表性不足群体的教育环境，而且可以改善所有学生的教育环境。这些方法将有两个组成部分，即非正规教育和正规教育。这种变化的非正式结构是一个名为“互动”的科学委员会。该委员会将整合未来科学、数学和工程（SME）专业人员面临的所有问题。潜在的主题将包括：社会动态（例如偏见），除了简历（或简历）之外建立社区的重要性，申请研究奖学金，学术奖学金和奖项的必要性，以及这些经历如何影响你的未来。互动将提供内部教育会议，并主持激励榜样，如杰出的女科学家、校友和该地区的科学家，他们已经走上了辉煌的职业生涯。互动也将促进同伴小组学习。中小企业学生认为，同伴小组学习的存在对提高中小企业专业学生的坚持性有最直接和最有效的贡献。正式部分是一门物理生物化学顶点课程，通过实验室捕捉跨专业主题的融合，并通过应用明确地将概念结合起来。生物化学与其他学科的联系将通过定量素养，语法是物理化学。侧重于实际结果的课程将强调女性在学习方面的特殊优势，因为有人认为许多其他学习策略本质上有利于男性的学习模式。学习策略的性别差异将通过多种解决问题的方法来平衡，并强调看似不同的主题之间的共性。

For the delivery of signaling molecules in a cell to occur, the membranes of the vesicle in which signaling molecules are packaged must fuse with another membrane. As timing is vital in cellular processes, this delivery of signaling molecules must be poised to trigger only when the appropriate signal or combinations of cellular signals transpire. Although this is a critical cellular event, how this regulated delivery occurs is not well understood. Membranes are comprised of a great diversity of lipids whose individual lipid-lipid interactions are weak and interactions within the membrane dictated by the lipids' chemical structure and its local milieu. These factors govern the resultant lipid's activity (effective concentration) and hence, how the membrane is targeted for binding to or partitioning into by proteins. Within this model, it is hypothesized that intrinsically weak interactions between lipids are critical for the system to reversibly and rapidly organize the protein clusters that modulate signaling. This offers a more nuanced regulation of biological events beyond a system dominated by a few, very strong interactions. These small interaction energies offer flexibility in how combinations of lipids, in response to proteins binding, form signaling platforms. This concept is hypothesized to be the basis for how key proteins involved in regulated delivery target distinct membranes. The objective of this project is to test the hypothesis that these key proteins are modulated not by a few strong interactions but by a necessary ensemble of weak interactions at the membrane. Testing will involve quantitative analysis and rigorous use of binding theory and thermodynamic (linkage) relationships by undergraduates from diverse scientific disciplines. New techniques, both conceptual and experimental, will also result from this project that will be applicable to many questions of biological relevance. The classic use of linkage relationships is an example of problem-based learning where biological processes are simply represented mathematically and interpreted. Each experiment becomes a case study and the derivation of equations is no longer restricted to assigned homework or to be used after years of graduate training. The goal is to demonstrate that undergraduates and young graduate students can propose, use, explore, and test these concepts. Broader Impacts The Broader Impacts of this project include the development of methodologies that will enhance the persistence, retention, and future success of women in scientific careers. By improving the educational environment for women, the educational environment not only for underrepresented groups but for all students will be improved. The methodologies will have two components, Informal and Formal Education. The Informal structure for this change is a scientific council, named Interactions. This council will integrate all issues that are faced by future science, mathematics and engineering (SME) professionals. Potential topics will include: social dynamics (e.g. bias), the importance of building a community in addition to a resume (or CV), the need to apply for research scholarships, academic scholarships and awards, and how these experiences can shape your future. Interactions will provide in-house educational meetings and host motivating role models such as distinguished female scientists, alumni, and scientists from the region who have gone on to illustrious careers. Interactions will also foster peer group learning. The existence of peer group learning has been identified by SME students as having the most immediate and most effective contribution to increasing persistence of students within SME majors. The Formal component is a Physical Biochemistry capstone course with laboratory capturing the convergence of topics across the major and explicitly uniting concepts through application. The linkage of biochemistry with other disciplines will be through quantitative literacy where the grammar is Physical Chemistry. A course focused upon practical outcomes will emphasize female specific advantages in learning as it is argued that many other learning strategies are inherently favorable to male learning patterns. Gender differences in learning strategies will be equalized through multiple approaches to problem solving, and the commonalities between seemingly diverse topics will be emphasized.