Engineering modular viral scaffolds for targeted bacterial population editing

Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to precisely manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic biology strategy to modulate phage host ranges by engineering phage genomes in Saccharomyces cerevisiae. We used this technology to redirect Escherichia coli phage scaffolds to target pathogenic Yersinia and Klebsiella bacteria, and conversely, Klebsiella phage scaffolds to target E. coli by modular swapping of phage tail components. The synthetic phages achieved efficient killing of their new target bacteria and were used to selectively remove bacteria from multi-species bacterial communities with cocktails based on common viral scaffolds. We envision this approach accelerating phage biology studies and enabling new technologies for bacterial population editing.

Synthesis of polyhydroxylated compounds from Derythrose: enzymatic inhibition studies

Dissertação de mestrado em Química Medicinal

Chronic prenatal depression and neonatal outcome

Four hundred and thirty pregnant women were recruited at approximately 22 weeks gestation at prenatal clinics. Of these, 86 (20%) were diagnosed as depressed. The women were seen again at approximately 32 weeks gestation and after delivery. Chronicity of depression was evidenced by continuing high depression scores in those women diagnosed as depressed. Comorbid problems were chronically high anxiety, anger, sleep disturbance, and pain scores. Less optimal outcomes for the depressed women included lower gestational age and lower birthweight of their newborns.