Biology subjects

Rodriguez Blanco, G.

Publications and source records attributed to Rodriguez Blanco, G..

4 recordsLinked to original sources

bioRxiv2024

Testing microbial biomining from asteroidal material onboard the International Space Station

Expanding human space exploration beyond Earths orbit necessitates efficient technologies for self-sustainable acquisition of local resources to overcome unviable resupply missions from Earth. Potential source of materials are asteroids, some of which contain valuable metals, such as platinum group elements. The BioAsteroid experiment, performed onboard the International Space Station, tested the use of microorganisms (bacteria and fungi) to carry out mining of useful elements from asteroidal material (L-chondrite) under microgravity, in support of a long-term human presence in space. The fungus Penicillium simplicissimum, enhanced the mean release of palladium, platinum and other elements from the meteorite material in microgravity, compared to non-biological leaching. However, there was large variability in the results. For many elements, non-biological leaching under microgravity was enhanced compared to terrestrial gravity, while bioleaching was unaffected. Metabolomics results revealed clear patterns that highlight the influence of space conditions on the microbial metabolism, particularly for P. simplicissimum. We identified the presence of carboxylic acids, and molecules of potential biomining and pharmaceutical interest, enhanced in microgravity. These results show a non-trivial effect of microgravity on bioleaching, highlighting the requirement of an optimal combination of microorganism(s), rock substrate, and conditions for successful biomining, both in space and Earth.

microbiology↗

bioRxiv2021

THEM6-mediated lipid remodelling sustains stress resistance in cancer

Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducing de novo sterol biosynthesis and preventing lipid-mediated induction of ATF4. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether, our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.

cancer biology↗

bioRxiv2020

Schlafen family member 5 (SLFN5) regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer

Androgen-deprivation therapy (ADT) is the standard of care for the treatment of non-resectable prostate cancer (PCa). Despite high treatment efficiency, most patients ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we perform a comparative proteomic analysis of three in vivo, androgen receptor (AR)-driven, orthograft models of CRPC. Differential proteomic analysis reveals that distinct molecular mechanisms, including amino acid (AA) and fatty acid (FA) metabolism, are involved in the response to ADT between the different models. Despite this heterogeneity, we identify SLFN5 as an AR-regulated biomarker in CRPC. SLFN5 expression is high in CRPC tumours and correlates with poor patient outcome. In vivo, SLFN5 depletion strongly impairs tumour growth in castrated condition. Mechanistically, SLFN5 interacts with ATF4 and regulates the expression of LAT1, an essential AA transporter. Consequently, SLFN5 depletion in CRPC cells decreases intracellular levels of essential AA and impairs mTORC1 signalling in a LAT1-dependent manner.

cancer biology↗

bioRxiv2019

Formate induces a metabolic switch in nucleotide and energy metabolism

Formate is a precursor for the de novo synthesis of purine and deoxythymidine nucleotides. Formate also interacts with energy metabolism by promoting the synthesis of adenine nucleotides. Here we use theoretical modelling together with metabolomics analysis to investigate the link between formate, nucleotide and energy metabolism. We uncover that endogenous or exogenous formate induces a metabolic switch from low to high adenine nucleotide levels, increasing the rate of glycolysis and repressing the AMPK activity. Formate also induces an increase in the pyrimidine precursor orotate and the urea cycle intermediate argininosuccinate, in agreement with the ATP dependent activities of carbamoyl-phosphate and argininosuccinate synthetase. In vivo data for mouse and human cancers confirms the association between increased formate production, nucleotide and energy metabolism. Finally, the in vitro observations are recapitulated in mice following intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism.

biochemistry↗