Keywords: COPASI; Dynamic metabolic modelling; Limonene; Parameter estimation; Time-series data.
ReadDengue (DENV) and Zika (ZIKV) viruses are important human pathogens belonging to the Flaviviridae family of RNA viruses. DENV is known to infect around 390 million people around the world annually [1], while ZIKV causes numerous diseases including microcephaly in infants [2]. Currently, limited treatments and vaccines are available and novel strategies and targets are urgently needed to develop therapeutics to treat these diseases. To achieve this, it is important to understand host factors and how they interact with DENV and ZIKV genomes during the viral life cycle.
ReadCOVID-19 vaccines have been essential in bringing the pandemic under control. They have shown to be highly efficacious against severe diseases
ReadThe mosquito-borne flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have established themselves as major human pathogens. Live attenuated vaccines are seen as the most effective method for preventing flavivirus infection. Flavivirus genome recoding has emerged as a next-generation vaccine development method that acts by rewriting the flavivirus genome. Previous flavivirus genome recoding attempts were based on deoptimising the flavivirus genome. However, these deoptimised flaviviruses were found to be attenuated in a species dependent manner. For example, deoptimised DENV and ZIKV did not demonstrate attenuation in mosquito cells or mosquito animal models, which is undesirable because these mosquito-borne flaviviruses should be attenuated in their mosquito vector to prevent vaccine escape. To overcome these limitations, we adopted a flavivirus genome recoding approach based on the contrary approach of optimising the flavivirus genome and applied it to DENV2 and ZIKV. We found that this genome recoding approach of codon optimisation could confer attenuation in both mouse and mosquito animal models. This indicates that our flavivirus genome recoding approach may be used as a reliable method to construct attenuated vaccine backbones for the mosquito-borne-flaviviruses in general.
ReadAlfatah et al. interrogate the relationship between glucose metabolism and TORC1 activation in Saccharomyces cerevisiae. They identify three distinct pathways for glucose-induced TORC1 activation, with each pathway requiring a different extent of glucose metabolism via the glycolytic pathway.
ReadFor many years, there has been general interest in developing virtual cells or digital twin models [1,2]. This is due to (i) a purely curiosity-driven need to build theories of life and, (ii) the potential to quickly and safely find cures for diseases by testing drugs in silico before testing them on actual organisms.
ReadThe selective targeting of mutated kinases in cancer therapies has the potential to improve therapeutic success and thereby the survival of patients. In the case of melanoma, the constitutively active MAPK pathway is targeted by a combinatorial inhibition of BRAF and MEK activities.
ReadUnbiased metagenomic sequencing is conceptually well-suited for first-line diagnosis as all known and unknown infectious entities can be detected, but costs, turnaround time and human background reads in complex biofluids, such as plasma, hinder widespread deployment.
Read