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Biology subjects

Lall, K.

Publications and source records attributed to Lall, K..

2 recordsLinked to original sources

Inducible Cooperation in a Synthetic Gut Bacterial Consortium Introduces Population Balance and Stability

In nature, microbes interact antagonistically, neutrally or beneficially. To shed light on the effects of positive interactions in microbial consortia we introduced metabolic dependencies and metabolite overproduction into four bacterial species. While antagonistic interactions govern the wildtype consortium behavior, the genetic modifications alleviated antagonistic interactions and resulted in beneficial interactions. Engineered cross-feeding increased population evenness, a component of ecological diversity, in different environments including in a more complex gnotobiotic mouse gut environment. Our findings suggest that metabolite cross-feeding could be used as a tool for intentionally shaping microbial consortia in complex environments.\n\nImportanceMicrobial communities are ubiquitous in nature. Bacterial consortia live in and on our body and in our environment and more recently, biotechnology is applying microbial consortia for bioproduction. As part of our body, bacterial consortia influence us in health and disease. Microbial consortia function is determined by its composition, which in turn is driven by the interactions between species. Further understanding of microbial interactions will help us deciphering how consortia function in complex environments and may enable us to modify microbial consortia for health and environmental benefits.

synthetic biology

Genomic underpinnings of lifespan allow prediction and reveal basis in modern risks

We use a multi-stage genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31, and identify and replicate novel findings near GADD45G, KCNK3, LDLR, POM121C, ZC3HC1, and ABO. We also validate previous findings near 5q33.3/EBF1 and FOXO3, whilst finding contradictory evidence at other loci. Gene set and tissue-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer -but not other cancers-explain the most variance, possibly reflecting modern susceptibilities, whilst cancer may act through many rare variants, or the environment. Resultant polygenic scores predict a mean lifespan difference of around five years of life across the deciles.

genomics