Modeling Influenza Antigenic Shift and Drift with LEGO Bricks

The significance of influenza virus for human health requires no introduction. Correspondingly, content related to the Influenza virus and its biology can be found in almost every microbiology and virology syllabus. Pedagogically, the influenza virus is an excellent choice for discussions of many key topics in microbiology/virology and their integration with issues in public health. The concepts of antigenic shift and drift are a classic example of influenza-related content in the classroom. They are central to understanding viral diversity and evolution and have direct application to vaccine design. Students often struggle to fully understand how both phenomena work mechanistically and thus have limited opportunity to gain an appreciation of the scientific principles behind the flu vaccine’s development and effectiveness. I have developed a simple exercise using conventional LEGO bricks to physically model antigenic shift and drift in order to aid student understanding. The exercise can be executed in any type and level of classroom for about 10 minutes and, if desired, extended to emphasize quantitative skills and molecular biology concepts or to trigger discussion of key issues in vaccine design. The manipulatives used are economical and easy to store, and pose no hazards in the classroom. No safety issues are associated with the described exercise

Dynamic Model Visualizing the Process of Viral Plaque Formation

In Microbiology and Virology courses, viral plaques are often presented to students as the way one can visualize viruses/bacteriophages. While students generally grasp the idea that counting plaques is essentially the same as counting viruses in their sample (assuming that one virus entering the cell is sufficient for productive infection), the process of plaque formation itself remains largely obscure. Many students fail to appreciate that viral plaques are actually a “laboratory-made” phenomenon allowing us to observe and study the growth of lytic viruses. The latter often presents a challenge for the interpretation of experimental data related to viral growth and drug discovery using plaque reduction assay. The hands-on model described here creates an opportunity for students to experience the process of viral plaque formation while engaging multiple senses and creating a lasting impression

eIF1A/eIF5B Interaction Network and its Functions in Translation Initiation Complex Assembly and Remodeling

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments

Topology and Regulation of the Human eIF4A/4G/4H Helicase Complex in Translation Initiation

SummaryThe RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. Remarkably, some of the interactions are continuously rearranged during the ATP binding/hydrolysis cycle of the helicase. We show that the accessory proteins modulate the affinity of eIF4A for ATP by interacting simultaneously with both helicase domains and promoting either the closed, ATP-bound conformation or the open, nucleotide-free conformation. The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning

Poster: Exploring Protein Synthesis as a Target for Anti-Cancer Drugs

Cancer is a diverse group of diseases presenting themselves as uncontrolled tumor growth. Chemotherapy and radiation combat cancer by introducing extensive damage to the genetic blueprint (DNA) of rapidly dividing cells and thus killing them. DNA damage is inflicted to normal cells to much lesser extent resulting in therapy side effects and increased risk of cancer re-occurrence. Rapidly dividing cancer cells exhibit higher rates of protein synthesis, presenting an alternative target for anti-cancer drugs. Since proteins are major building blocks of living cells, inhibiting protein synthesis will cease cell growth and rapid division, thus slowing down/stopping cancer without damaging DNA. This project presents first steps in developing a screen for inhibitors of protein synthesis disrupting protein-protein interactions critical for the initiation of the process

Poster: Scientific Discovery in a Fast-Forward Mode: Getting Personal and Creative with Virtual Viruses

Virtual virus is a semester-long project modeling the process of scientific discovery, offered as a part of the BIOL450/Virology course. Students were challenged to apply virology concepts to synthesize their own virus in a series of hands-on sessions and mini-projects. Each student built a physical model and developed a virtual scenario as to how their virus interacted with the host body. The project results were communicated via class presentation and a report in the format of scientific review article. Project outcomes demonstrated high level of student engagement as identified by the personal dimensions of the developed virtual viruses and the quality of the produced work. Analysis of student work demonstrates that the virtual virus project is a successful model for capstone experience in biology