Medina, J. S. | bioRxiv Science

bioRxiv2022

Biomass generation and heterologous isoprenoid milking from engineered microalgae grown in anaerobic membrane bioreactor effluent

1.Wastewater (WW) treatment in anaerobic membrane bioreactors (AnMBR) is considered more sustainable than in their aerobic counterparts. However, outputs from AnMBR are mixed methane and carbon dioxide gas streams as well as ammonium- (N) and phosphate- (P) containing waters. Using AnMBR outputs as inputs for photoautotrophic algal cultivation can strip the CO2 and remove N and P from effluent which feed algal biomass generation. Recent advances in algal engineering have generated strains for concomitant high-value side product generation in addition to biomass, although only shown in heavily domesticated, lab-adapted strains. Here, investigated whether such a strain of Chlamydomonas reinhardtii could be grown directly in AnMBR effluent with CO2 at concentrations found in its off-gas. The domesticated strain was found to proliferate over bacteria in the non-sterile effluent, consume N and P to levels that meet general discharge or reuse limits, and tolerate cultivation in modelled (extreme) outdoor environmental conditions prevalent along the central Red Sea coast. High-value co-product milking was then demonstrated, up to 837 g L-1 culture in 96 h, in addition to algal biomass production, [~]2.4 g CDW L-1 in 96 h, directly in effluents. This is the first demonstration of a combined bio-process that employs a heavily engineered algal strain to enhance the product generation potentials from AnMBR effluent treatment. This study shows it is possible to convert waste into value through use of engineered algae while also improve wastewater treatment economics through co-product generation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/510234v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@a7e325org.highwire.dtl.DTLVardef@31c0a2org.highwire.dtl.DTLVardef@5deea8org.highwire.dtl.DTLVardef@df672b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2019

Oncologic Therapy Shapes the Fitness Landscape of ClonalHematopoiesis

Clonal hematopoiesis (CH) is frequent in cancer patients and associated with increased risk of therapy related myeloid neoplasms (tMN). To define the relationship between CH, oncologic therapy, and tMN progression, we studied 24,439 cancer patients. We show that previously treated patients have increased rates of CH, with enrichment of mutations in DNA Damage Response (DDR) genes (TP53, PPM1D, CHEK2). Exposure to radiation, platinum and topoisomerase II inhibitors have the strongest association with CH with evidence of dose-dependence and gene-treatment interactions. We validate these associations in serial sampling from 525 patients and show that exposure to cytotoxic and radiation therapy imparts a selective advantage specifically in hematopoietic cells with DDR mutations. In patients who progressed to tMN, the clone at CH demarcated the dominant clone at tMN diagnosis. CH mutational features predict risk of therapy-related myeloid neoplasm in solid tumor patients with clinical implications for early detection and treatment decisions.

genetics↗