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Transport Proteins on Strike: Causes, Consequences, and Solutions

The transport proteins that carry those molecules across the membrane via facilitated diffusion are specific for those molecules. Glucose transport proteins only carry glucose in and amino acid transport proteins only carry amino acid in.

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This role-play case study teaches students about plasma membrane transport and the functions of transport proteins in the phospholipid bilayer. Students act out the parts of molecules and structures in a fantastical cellular world where the unionized transport proteins have called for a work stoppage. The concepts of diffusion, facilitated diffusion, osmosis, and active transport are discussed. Written for an undergraduate non-majors human biology course, the case is also suitable for general biology, cell biology, anatomy and physiology, and high school biology.

While there are several available lessons for teaching introductory biology students about diffusion, facilitated diffusion, and active transport, fewer materials exist to support upper-division students' understanding of the proteins that mediate these forms of transport. In the 1970s, mitochondrial pyruvate carrier (MPC) proteins were predicted to import pyruvate from the cytoplasm into mitochondria for cellular respiration. Yet it was not until 2012 that the identity of the proteins responsible for this transport was confirmed in two seminal publications. In this Lesson, students will use their background knowledge of transport mechanisms to analyze data from those papers to determine which of the predicted MPC proteins are actually part of the mitochondrial pyruvate transporter. Student will also learn how scientists test whether a protein is necessary and sufficient. The Lesson is written in the style of process-oriented guided inquiry learning (POGIL). POGIL is a teaching approach that requires students to work collaboratively in small groups to answer a set of questions based on scientific data. Questions in the POGIL activity, called the problem set, are structured so that each question leads to the next, helping to guide students to a deeper understanding of the content. During this Lesson, the instructor acts as a facilitator to guide student learning. Several forms of assessment are included within the Lesson, allowing instructors to assess learning gains. This Lesson has been used multiple times by over 10 faculty in an upper-division Cell Biology course and can also be used in other upper-division biology courses.

The cell's ability to selectively transport molecules across its membranes is critical for its survival. Whether transport of molecules occurs across the cell membrane or the membranes of organelles, regulation of molecular gradients is important for proper cellular function. Thus, life science students need a broad understanding of transport mechanisms such as diffusion, facilitated diffusion, and active transport, as well as the proteins that mediate these mechanisms.

Lessons exist for helping introductory biology students understand the basics of membrane transport. These lessons rely on role playing (1-3), computer simulations (4), case studies (5), and analysis of classic papers in the primary literature (6). Our lesson differs from existing lessons in three major ways. First, our lesson was specifically developed for upper-division biology students rather than introductory biology students. We wanted students in our upper-division Cell Biology course to use their basic understanding of membrane transport concepts to gain a deeper understanding of the mechanisms involved. Second, we designed our lesson so that students would learn how scientists identify the proteins that are responsible for transport of a molecule using biochemical and genetic experiments. We also wanted students to understand how scientists use results from more than one organism to confirm the identity of transport proteins. Third, we created a lesson that draws on an approach for small-group learning called Process-Oriented Guided Inquiry Learning (POGIL) (7).

We used two seminal studies published back-to-back in Science that revealed the identity of the long unknown mitochondrial pyruvate carrier (MPC), a transporter that brings pyruvate into the mitochondrial matrix from the cytoplasm (8,9). We selected key figures from the papers to give students practice analyzing real data while drawing on their pre-requisite knowledge from biochemistry and genetics. The studies from the papers serve as models to help students understand how to design experiments for confirming whether other proteins serve as transporters for particular molecules. We created a Lesson in the spirit of POGIL, similar to our previous POGIL-inspired Lesson on protein localization methods (10).

The activity effectively meets the stated learning goals and objectives. Students perform well on summative assessment related to this Lesson. When we have given matched-pair questions on the corresponding unit exam, nearly all students are able to correctly interpret graphs with data from transport mutants. Most students are able to correctly determine whether proteins are necessary or sufficient for transport. The majority of students can also apply their understanding of pyruvate transport to a more challenging question that asks them to explain the effect of an ionophore on pyruvate transport. Student have also performed well when we have given matched-pair questions on a cumulative final exam or an in-class assessment three months after completing the Lesson. Yet some student confusion is revealed about what type of experiment allows a scientist to make conclusions about sufficiency of a protein or proteins for transport. This suggests that time should be spent revisiting the concept of how to test for sufficiency in order to promote long-term understanding.

Students respond positively to the Lesson based on classroom observation by multiple instructors and student participation during class discussion. Instructors who have taught the Lesson note that students struggle at first to understand the difference between necessity and sufficiency, but they become more comfortable after answering the questions and hearing the class discussion. Students seem to be pleased when these concepts finally "click." Students also appear excited to analyze the pedigree data and some students have explained that this is because they appreciate the connection between pyruvate transport and human health. Students seem to enjoy applying their prior knowledge of pedigree analysis, which they learned in the pre-requisite Genetics course, during the Lesson. When we've taught the Lesson in our Cell Biology course, our students readily volunteer to share their answers with the class.

In 2017, Theresa May's government implemented the Trade Union Act, which sought to reduce strikes by 35 percent in public services like transport, health and education through tougher ballot thresholds for industrial action.

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