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The collection of proteins within a cell determines its health and function. Proteins are responsible for nearly every task of cellular life, including cell shape and inner organization, product manufacture and waste cleanup, and routine maintenance. Proteins also receive signals from outside the cell and mobilize intracellular response. They are the workhorse macromolecules of the cell and are as diverse as the functions they serve.

This flipped case was designed to introduce students in a general introductory biology course to basic protein structure. The two videos and interrupted case use keratins in hair as model proteins. From the videos students learn how amino acids regulate protein structure, and how small changes in amino acid sequence have large impacts on overall protein organization and function. The case story focuses on a puppy whose hair changes from straight to curly when it sheds its coat. The protagonist tests the adult versus puppy hair, and discovers that the amino acid composition is different in the curly versus straight hair samples. Students apply basic principles of protein structure to hypothesize why the dog's coat switched from straight to curly. The case intentionally stops short of providing a complete answer to the mystery, so students think through the molecular processes logically rather than having a final "correct" answer. An optional activity is provided that makes the case more appropriate for an introductory cell biology class.

This directed case study examines the molecular basis of cystic fibrosis to emphasize the relationship between the genetic code stored in a DNA sequence and the encoded protein's structure and function. Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein that functions to help maintain salt and water balance along the surface of the lung and gastrointestinal tract. This case introduces students to "Maggie," who has just been diagnosed with cystic fibrosis. The students must identify the mutation causing Maggie's disease by transcribing and translating a portion of the wildtype and mutated CFTR gene. Students then compare the three-dimensional structures of the resulting proteins to better understand the effect a single amino acid mutation can have on the overall shape of a protein. Students also review the concepts of tonicity and osmosis to examine how the defective CFTR protein leads to an increase in the viscosity of mucus in cystic fibrosis patients. This case was developed for use in an introductory college-level biology course but could also be adapted for use in an upper-level cell or molecular biology course.

Current CRISPR-based screens often mutate the beginning of a gene, which sometimes results in the expression of a functional protein variant. To circumvent this problem, researchers at Cold Spring Harbor Laboratory (CSHL) designed CRISPR guide RNAs that would mutate the portion of a gene encoding a domain on the surface of the protein where a small molecule could bind to alter the protein's function. The team had previously identified such a binding pocket on the protein BRD4, and a small molecule inhibitor that binds in the pocket is an effective leukemia treatment.

Protein folding and trafficking is essential for normal cell function, and when it goes awry it can lead to various chronic conditions, including fatty liver disease, diabetes, and Parkinson's. The narrative of this case study follows two undergraduate students engaged in a summer research project evaluating the effects of cell stress on cell function and health in the model organism Caenorhabditis elegans (C. elegans).  During the case study, students review animal cell organelle function and then learn about endoplasmic stress and unfolded protein response. Prior knowledge needed for the case is basic animal cell organelles and their functions and use of model organisms in research. The case was designed for a flipped classroom in which students prepare in advance by taking a quiz and watching two videos; a PowerPoint animation is also included.

Venom - information on protein structure and function, following scenario of a scorpion bite.  Interactive game and activities included on site.

This case study synthesizes students' knowledge of the central dogma and cell structure by examining a rare health disorder in order to understand protein targeting and its medical consequences. Students first identify the molecular alteration in affected members of a family with renal Fanconi syndrome as reported in the New England Journal of Medicine (2014). Students then use an online bioinformatics tool to analyze the wildtype and mutant proteins and examine their subcellular localization. Finally, students use this information to explain the symptoms of affected family members. The case is delivered with a PowerPoint presentation that includes a selection of brainstorming prompts and "clicker questions." Students complete a worksheet (included in the teaching notes) before class, making the activity suitable for a flipped classroom. A second worksheet (also included in the teaching notes) is completed during class. The case is written for an introductory biology course for majors, but could also be used as a unit capstone in a non-majors human biology course; the case is also scalable to upper division courses in physiology that specifically explore kidney function.

She wanted to understand the effects of mutations that the gene for p53 is prone to. In dozens of simulations, she and her colleagues tracked how common p53 mutations further destabilize the already floppy protein, distorting it and preventing it from binding to DNA. Some simulations also revealed something else: a fingerhold for a potential drug. Once in a while, a small cleft forms in the mutated protein's core. When Amaro added virtual drug molecules into her models, the compounds lodged in that cleft, stabilizing p53 just enough to allow it to resume its normal functions.

The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the "viral supergroup" and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts.

Because the gene-enzyme system forms a closed loop, it presents us with a classic chicken or egg conundrum: Which came first, genes or the protein enzymes they code for? While the details are still not fully worked out, discoveries over the past few decades have lead researchers to a surprising possible solution: What really came first? Genes that act as enzymes! The RNA World Hypothesis is the idea that before living cells, the genetic code, and the gene/protein cycle ever existed, chains of a chemical called RNA were forming naturally. Once formed, some of these chains were able to function as enzymes, and were even able to evolve by making copies of themselves with slight, accidental modifications.

Panobinostat is a new type of drug that works by blocking an enzyme responsible for modifying DNA at the epigenetic level. Epigenetics refers to chemical marks on DNA itself or on the protein "spools" called histones that package DNA. These marks influence the activity of genes without changing the underlying sequence, essentially acting as volume knobs for genes. Earlier genomic studies showed that about 80 percent of DIPG tumors carry a mutation that alters a histone protein, resulting in changes to the way DNA is packaged and tagged with those chemical marks. This faulty epigenetic regulation results in activation of growth-promoting genes that should have been turned off, and shutdown of others that should have acted as brakes to cell multiplication. Cancer is the result. Panobinostat appears to work by restoring proper functioning of the cells' chemical tagging system.

3:35 video To some they look like bow-legged cowboys. To others, swaggering pirates. Either way, the two-legged molecules known as motor proteins are what get the job of living done in most of your cells.

One of the most important molecules relating to cancer is called p53. This Click and Learn explains the structure and function of the p53 protein as well as how the protein's activity is regulated. Learn why p53 is called the guardian of the genome and how interfering with its function can lead to cancer.

Taylor must write a report about a natural toxin while she is home from college on break. After a family dinner conversation about the latest attempt to poison a politician via a letter, Taylor decides to explore how ricin acts as a poison. Students work in small groups to help Taylor by working through figures from primary literature papers and exploring the use of an in vitro translation system, sucrose gradient fractionation and the effect of inhibiting various steps of translation.  A shorter, second day activity involves students looking further at the effect of ricin upon ribosome function and at the ricin protein itself.  Students individually complete a cumulative assignment of writing a letter back to Mom and Dad about how ricin has its effects. This case was designed for use in a second semester biochemistry course or a molecular biology course that incorporates the mechanism of transcription. Prerequisite knowledge includes a general understanding of the steps of translation and the ability to interpret data from agarose gels.

In this case, developed for an introductory genetics class, students meet a woman whose family has a history of colon cancer. Students create a pedigree based on information from the case and discuss what it means to be genetically predisposed to cancer. Using bioinformatics tools from the NCBI database, students identify and examine the mutation in the woman's APC gene that results in genetic predisposition to colon cancer. Finally, they investigate the biological function of the APC protein to understand why this mutation contributes to the development of cancer and determine whether APC is a proto-oncogene, tumor suppressor gene, or genome stability gene.

de Villena and his colleagues counted the RNA molecules produced and found that genes from the father produced on average more RNA than genes from the mother. (And remember, RNA directs the production of proteins, which are the workhorses of the body's development and function.) The implication? "It's not only what you inherit, but from whom you inherit," he said.

Why does a snake have 25 or more rows of ribs, whereas a mouse has only 13? The answer, according to a new study, may lie in "junk DNA," large chunks of an animal's genome that were once thought to be useless. The findings could help explain how dramatic changes in body shape have occurred over evolutionary history. Scientists began discovering junk DNA sequences in the 1960s. These stretches of the genome-also known as noncoding DNA-contain the same genetic alphabet found in genes, but they don't code for the proteins that make us who we are. As a result, many researchers long believed this mysterious genetic material was simply DNA debris accumulated over the course of evolution. But over the past couple decades, geneticists have discovered that this so-called junk is anything but. It has important functions, such as switching genes on and off and setting the timing for changes in gene activity. 

The DNA in just one of your cells gets damaged tens of thousands of times per day. Because DNA provides the blueprint for the proteins your cells need to function, this damage can cause serious issues-including cancer. Fortunately, your cells have ways of fixing most of these problems, most of the time. Monica Menesini details the processes of DNA damage and repair.

This flipped case study tells the story of Joyce, a biology student who notices the development of some unusual symptoms (foot slapping and slurred speech) in her mother. In an effort to understand the cause, Joyce views a documentary-style trigger video (created by the case author) that suggests to Joyce that her mom may in fact have amyotrophic lateral sclerosis or ALS. The rest of the case walks Joyce through understanding how normal neurons compare to neurons in ALS patients and how that might affect muscle function. The case explores the link between genes, particularly SOD-1, to the formation of malformed proteins and its potential role in the development of ALS. The case concludes with a discussion of drug development and highlights the timeline and costs associated with drug discovery as Joyce becomes concerned about the lack of drugs in the pipeline for ALS, which her mother is ultimately diagnosed with. The case is appropriate for a number of classes including general biology, biotechnology, anatomy and physiology, upper level-cell biology, or any human health and disease-related course.

This case study examines the structure of hemoglobin and myoglobin and how the structure of these molecules dictates their function. The case is written as a play in which several candidates have responded to a help wanted ad seeking an employee with a strong work ethic, round-the-clock availability, and the capacity to carry oxygen in the human body and deliver it in a timely fashion when needed. The successful candidate also needs to carry a heavy load of carbon dioxide and dispose of it according to waste disposal regulations and be willing to work with human resources regarding salary and benefits.