Showing papers by "Mark P. Styczynski published in 2017"
TL;DR: This work presents a proof of principle for the development of low-cost, minimal-equipment, field-deployable biosensors for nutritional epidemiology applications, and presents approaches to overcome innate immune responses that would otherwise hinder bacterial sensor survival.
Abstract: Deficiencies in vitamins and minerals (micronutrients) are a critical global health concern, in part due to logistical difficulties in assessing population micronutrient status. Whole-cell biosensors offer a unique opportunity to address this issue, with the potential to move sample analysis from centralized, resource-intensive clinics to minimal-resource, on-site measurement. Here, we present a proof-of-concept whole-cell biosensor in Escherichia coli for detecting zinc, a micronutrient for which deficiencies are a significant public health burden. Importantly, the whole-cell biosensor produces readouts (pigments) that are visible to the naked eye, mitigating the need for measurement equipment and thus increasing feasibility for sensor field-friendliness and affordability at a global scale. Two zinc-responsive promoter/transcription factor systems are used to differentially control production of three distinctly colored pigments in response to zinc levels in culture. We demonstrate strategies for tuning ...
51 citations
TL;DR: A model-based interpretation of expression data of genes coding for enzymes associated with purine metabolism obtained during infections of rhesus macaques with the malaria parasite reveals clear patterns of flux redistribution within the purine pathway that are consistent between the two malaria pathogens.
20 citations
TL;DR: The possibility that malarial anaemia may be driven by monocyte-associated disruption of GATA1/GATA2 function in erythroid progenitors resulting in insufficient erythropoiesis during acute infection is suggested.
Abstract: Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax malaria) that may affect erythropoiesis. An appropriate erythropoietic response did not occur to compensate for anaemia during acute cynomolgi malaria despite an increase in erythropoietin levels. During this period, there were significant perturbations in the bone marrow transcriptome. In contrast, relapses did not induce anaemia and minimal changes in the bone marrow transcriptome were detected. The differentially expressed genes during acute infection were primarily related to ongoing inflammatory responses with significant contributions from Type I and Type II Interferon transcriptional signatures. These were associated with increased frequency of intermediate and non-classical monocytes. Recruitment and/or expansion of these populations was correlated with a decrease in the erythroid progenitor population during acute infection, suggesting that monocyte-associated inflammation may have contributed to anaemia. The decrease in erythroid progenitors was associated with downregulation of genes regulated by GATA1 and GATA2, two master regulators of erythropoiesis, providing a potential molecular basis for these findings. These data suggest the possibility that malarial anaemia may be driven by monocyte-associated disruption of GATA1/GATA2 function in erythroid progenitors resulting in insufficient erythropoiesis during acute infection.
20 citations
TL;DR: The approaches used here demonstrate the disconnect between fluorescent and metabolite reporters, help enable the use of lycopene as a reporter, and are likely generalizable to other systems that require precise control of metabolite production.
19 citations