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Using Open Access papers as a teaching tool

6 May 2022

Two key aspects of scientific training are learning to think critically about the literature and developing a good writing style. Professor Guy Caldwell is a researcher at the University of Alabama who leverages articles from our Open Access journal Disease Models & Mechanisms for this purpose.

Guy challenges his graduate students to select a paper published recently in Disease Models & Mechanisms and to write a research highlight about. Here, we take a look at two research highlights that were produced by students Katelyn Senkus and Melanie Mew.  

 

Which came first (in TDP-43 proteinopathies), the protein depletion or the aggregation?’, a research highlight by Katelyn Senkus

For her research highlight, Katelyn Senkus wrote about a paper from Miriam Pacetti, Laura De Conti et al. that investigates the role of a protein called TDP-43 in neurodegenerative disease. Katelyn began by detailing the significance of this protein: “Neurodegenerative diseases encompass a range of conditions, each with a unique pathophysiology and manifestation of symptoms. Although seemingly disparate, conditions like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration share a key underlying feature, TDP-43 abnormalities, and are classified as TDP-43 proteinopathies”.

TDP-43 is a nuclear protein with key roles in transcriptional repression and exon skipping activation. Katelyn explained that, in disease conditions, “TDP-43 can form cytoplasmic aggregates that deleteriously affect neuronal health”. This aggregation causes TDP-43 to be depleted from the nucleus. However, it was unclear whether nuclear depletion is a consequence or a cause of the disease.

Katelyn noted that Pacetti, De Conti et al. quantified the levels of TDP-43 “in various tissues of 10- and 90-day-old mice. Significant reductions in TDP-43 mRNA and protein were observed in brain tissue from 90-day-old mice, but not liver tissue”. It seemed that this decrease was associated with certain epigenetic modifications at the promoter of the TDP-43 gene.

The researchers moved in vitro to test the effect of inducing these epigenetic modifications in motor neuron-derived NSC-34 cells. “Following induction of hypomethylation, significant increases in TDP-43 mRNA and protein levels were observed,” Katelyn explained, “whereas hypermethylation significantly reduced promoter activity”. Similar results were obtained in human cell lines, which highlights the translational potential of this work.

The authors postulate that variations in the levels of epigenetic modification between individuals may contribute to variations in likelihood of ALS onset. Summarising the significance of the paper, Katelyn concluded that “the current study results have the potential to significantly impact public health through development of epigenetic-targeted therapies”.

 

Glassy eyes: A new transgenic Drosophila model for exploring human prion protein toxicity’, a research highlight by Melanie Mew

Melanie Mew’s research highlight focused on a study from Ryan Myers et al. that presents a new Drosophila model for studying prions.

Prions are misfolded proteins that can cause other proteins to also misfold. They are perhaps most famous for being the cause of bovine spongiform encephalopathy (or ‘mad cow’ disease) and are always fatal. As Melanie explained in her article, “a major challenge to studying prion diseases is that they occur only in mammals, whose long generation times and high maintenance costs limit the speed and statistical power of research”.

To combat this, Myers and colleagues generated a Drosophila model expressing mammalian prion proteins. In her research highlight, Melanie discussed how the expression of human prions resulted in smaller, ‘glassy’ eyes in the flies. Meanwhile, flies expressing mouse prions had comparatively normal eyes. This suggested that human prions are more toxic than rodent prions.

The researchers found that they could rescue the glassy eye phenotype induced by human prions if they modulated certain proteins involved in the unfolded protein response (UPR) pathway.  “Activating the PERK branch of the UPR or inhibiting the Ire1α branch could be valuable treatment strategies for prion diseases,” Melanie summarised in her research highlight. “Other therapeutic options could include modulating the structure of the prion protein itself. In this vein, Myers and colleagues investigated the protective effects of different amino acid substitutions found in dogs, horses, rabbits, and pigs. Asp167Ser, the canine residue mutation was protective against eye disorganisation and mushroom body degeneration in flies”.

A gallery of fruit fly eyes viewed under a microscope
A gallery of fly eye phenotypes from the paper Melanie Mew highlighted. Here, the flies express different unfolded protein response alleles, either alone or in combination with human prion protein.

 

The students appreciated the opportunity to summarise the work of other researchers. “I enjoyed the challenge of trying to honour the complexity of biological systems and experiments while highlighting only the most compelling results of the research study,” Melanie said, as she reflected on what she had gained from the experience of writing her research highlight. “This exercise in summary and synthesis gave me a greater appreciation for the simple yet profound insights that can be gleaned from studying evolutionary changes and relationships”.

Katelyn also relished the experience. “I always enjoy reading recently published articles to keep current with my research area and other topics of priority,” she said. “While I’m a nutrition scientist by training, distilling the current scientific paper into a shorter summary was a welcome challenge since there is considerable overlap in research methodology among scientific disciplines. I applied my prior knowledge about epigenetic processes to a new biological concept, and I left with a more robust understanding of the mechanism as well as potential ideas for interdisciplinary research collaborations”.

Guy’s class is a great example of how Open Access research can be used as a teaching tool. preLights, our preprint highlighting service, has also been used as an educational resource for group-based critical analysis of preprints. If you teach graduate classes that touch on any of these issues, we encourage you to give something like this a try.


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