In this article the authors created an interaction map of proteins involved in colorectal cancer to look for driver vs. non-driver genes. That is they wanted to see if they could determine what genes are more likely to drive the development and progression in colorectal cancer and which are present in altered states but not necessarily driving disease progression.
DegS is an integral inner membrane protein in E. coli that helps break down misfolded proteins. When it is mutated, there is a large increase in the production of outer membrane vesicles (OMVs), which are thought to play a role in pathogenesis. This study used mutant strains of uropathogenic E. coli (UPEC) to characterize the role of DegS and OMVs on UPEC virulence.
In order for cells to successfully multiply, a number of proteins are needed to correctly coordinate the replication and division process. In this study, students use fluorescence microscopy and molecular methods to study CCDC11, a protein critical in the formation of cilia. Interestingly, they uncover a new role for CCDC11, critical in the cell division across multiple human cell lines.
With disruption of DNA repair pathways pertinent to the timeline of cancer, thorough evaluation of mutations relevant to DNA repair proteins is crucial within cancer research. One such mutation includes S815L PMS2 - a mutation that results in significant decrease of DNA repair function by PMS2 protein. While mutation of PMS2 is associated with significantly increased colorectal and endometrial cancer risk, much work is left to do to establish the functional effects of the S815L PMS2 mutation in ovarian cancer progression. In this article, researchers contribute to this essential area of research by uncovering the tumor-progressive effects of the S815L PMS2 mutation in the context of ovarian cancer cell lines.
Alzheimer's disease is one of the leading causes of death in the United States and is characterized by neurodegeneration. Mishra et al. wanted to understand the role of two transport proteins, LRP1 and AQP4, in the neurodegeneration of Alzheimer's disease. They used a model organism for Alzheimer's disease, the nematode C. elegans, and genetic engineering to look at whether they would see a decrease in neurodegeneration if they increased the amount of these two transport proteins. They found that the best improvements were caused by increased expression of both transport proteins, with smaller improvements when just one of the proteins is overly expressed. Their work has important implications for how we understand neurodegeneration in Alzheimer's disease and what we can do to slow or prevent the progression of the disease.
Cutibacterium acnes is a bacterium believed to play an important role in the pathogenesis of common skin diseases such as acne vulgaris. Currently, acne is known to be associated with strains from the type IA1 and IC clades of C. acnes, while those from the type IA2, IB, II, and III phylogroups are associated with skin health. This is the first study to explore the sequence space of individual gene products of different C. acnes phylogroups. Our analysis compared the sequence space topology of virulence factors to proteins with unknown functions and housekeeping proteins. We hypothesized that sequence space features of virulence factors are different from housekeeping protein features, which potentially provides an avenue to deduce unknown proteins’ functions. This proposition should be confirmed based on further experimental outcomes. A notable similarity in the sequence spaces’ topological features of previously known as housekeeping proteins encoded by recA and guaA genes to ‘putative virulence’ genes camp2 and tly was observed. Our research suggests further investigation of recA and guaA’s potential virulence properties to better understand acne pathogenesis and develop more targeted acne treatments.
The Wnt signaling pathway, known to coordinate important aspects of cellular homeostasis ranging from differentiation, proliferation, migration, and much more, is dysregulated in many human diseases. This study demonstrates that aminomethylphosphonic acid, which is the main metabolite found in the common herbicide Glyphosate, is toxic to planaria and capable of binding to canonical Wnt proteins.
Enzyme chemotaxis is a thermodynamic phenomenon in which enzymes move along a substrate concentration gradient towards regions with higher substrate concentrations and can be used to steer nanovehicles towards targets along natural substrate concentrations. In patients with Alzheimer’s disease, a gradient of tau protein forms in the bloodstream. Tau protein is a substrate of the enzyme CDK5, which catalyzes the phosphorylation of tau protein and can travel using chemotaxis along tau protein gradients to increasing concentrations of tau and amyloid-beta proteins. The authors hypothesized that CDK5 would be able to overcome these barriers of Brownian motion and developed a quantitative model using Michaelis-Menten kinetics to define the necessary parameters to confirm and characterize CDK5’s chemotactic behavior to establish its utility in drug delivery and other applications.
Catalase is a critical enzyme in the human body because it is capable of converting potentially dangerous hydrogen peroxide into water and oxygen. This work asks whether ethanol affects catalase activity, as alcohol consumption has been often linked to hepatitis occurring in the liver, where catalase level is especially high, and ethanol is known to be capable of denaturing proteins. Testing different concentrations of ethanol found that higher concentrations reduced the activity of catalase. This work has important implications on the negative effects of ethanol on metabolism, in which catalase plays an important role, and protein function more broadly.
In this article the authors address the complex and life quality-diminishing neurodegenerative disease known as Parkinson's. Although genetic and/or environmental factors contribute to the etiology of the disease, the diagnostic symptoms are the same. By genetically modifying fruit flies to exhibit symptoms of Parkinson's disease, they investigate whether drugs that inhibit mitochondrial calcium uptake or activate the lysosomal degradation of proteins could improve the symptoms of Parkinson's these flies exhibit. The authors report the most promising outcome to be that when both types of drugs were used together. Their data provides encouraging evidence to support further investigation of the utility of such drugs in the treatment of human Parkinson's patients.