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Alberti, G.

Publications and source records attributed to Alberti, G..

4 recordsLinked to original sources

A humanized ossicle platform for real-time tracking and preclinical assessment of CAR-based immunotherapies in acute myeloid leukemia

Preclinical evaluation of chimeric antigen receptor (CAR)-T therapies for acute myeloid leukemia (AML) is limited by the lack of models that faithfully recapitulate the human bone marrow (BM) niche. Here, we implemented a humanized ossicle-based AML model that enables simultaneous engraftment of leukemic blasts and longitudinal assessment of responses to CAR-based immunotherapies. Intravenous or intra-ossicle injection of AML blasts produced robust, reproducible disease mimicking features of human AML within its microenvironment. To monitor tumor burden and immune effector cells in real-time, we developed a dual bioluminescence system using distinct luciferases in AML and CAR-T cells. This approach allowed non-invasive longitudinal tracking of CAR-T cell localization, expansion, persistence, and leukemic clearance within the ossicle. Overall, our model provides a powerful platform to study CAR-T cell behavior within a human BM niche and, for the first time, allows simultaneous longitudinal visualization of leukemic burden and CAR-T cell dynamics in a physiologically relevant ossicle-based AML model. TeaserHumanized ossicles combined with dual BLI enable tracking of AML progression and CAR-T cell dynamics in a human stromal niche.

Cell Biology↗

The ideotype for drought tolerance in bioenergy Populus nigra

Fast-growing perennial trees such as Populus nigra L. are important species for wood, plywood, pulp, and bioenergy feedstock production, yet tree vigor in a changing climate is poorly understood. This research aimed to identify breeding targets for yield in water-limited environments, alongside unraveling the relationship between drought, yield, and glucose release in P. nigra. A diversity panel of 20 P. nigra genotypes, selected from a wide natural association population, was grown at three divergent European sites. Through extensive phenotyping of physiological and morphological productivity and water-use traits, under irrigated conditions and when exposed to a progressive drought, we elucidated the adaptive and plastic drivers underlying tree productivity. We have identified the underpinning traits for drought tolerance, whereby high yields can be maintained under water deficit, in this key species. This highlighted the importance of examining the yield stress index (YSI) over the drought resistance index (DRI) to assess genotypes for performance under moderate drought. In this way, we found genotypes with high hydraulic capacity, and large leaves made up of many cells to be best suited to multiple European environments, with contrasting water availability. Moreover, we identified genotypes that combine yield and water use efficiency, with good glucose release potential, which will be important traits for the future of poplar as a bioenergy crop. Vigorous poplar genotypes, which are adapted to wet climates showed high environmental plasticity. However, in European drought scenarios, these trees outperform drought resistant genotypes, and some exhibit good glucose release. These trees are a valuable resource for the future.

plant biology↗

Artificial selection optimizes pollutant-degrading bacterial communities

Artificial selection is a promising way to improve microbial community functions, but previous experiments have only shown moderate success. Here, we experimentally evaluate a new method that was inspired by genetic algorithms to artificially select small bacterial communities of known species composition based on their degradation of an industrial pollutant. Starting from 29 randomly generated four-species communities, we repeatedly grew communities for four days, selected the 10 best-degrading communities, and rearranged them into 29 new communities composed of four species of equal ratios whose species compositions resembled those of the most successful communities from the previous round. The best community after 18 such rounds of selection degraded the pollutant better than the best community in the first round. It featured member species that degrade well, species that degrade badly alone but improve community degradation, and free-rider species that did not contribute to community degradation. Most species in the evolved communities did not differ significantly from their ancestors in their phenotype, suggesting that genetic evolution plays a small role at this time scale. These experiments show that artificial selection on microbial communities can work in principle, and inform on how to improve future experiments.

evolutionary biology↗

Microbial invasion of a toxic medium is facilitated by a resident community but inhibited as the community co-evolves

Predicting whether microbial invaders will colonize an environment is critical for managing natural and engineered ecosystems, and controlling infectious disease. Invaders often face competition by resident microbes. But how invasions play out in communities dominated by facilitative interactions is less clear. We previously showed that growth medium toxicity can promote facilitation between four bacterial species, as species that cannot grow alone rely on others to survive. Following the same logic, here we allowed other bacterial species to invade the four-species community, and found that invaders could more easily colonize a toxic medium when the community was present. In a more benign environment instead, invasive species that could survive alone colonized more successfully when the residents were absent. Next, we asked whether early colonists could exclude future ones through a priority effect, by inoculating the invaders into the resident community only after its members had co-evolved for 44 weeks. Compared to the ancestral community, the co-evolved resident community was more competitive toward invaders, and less affected by them. Our experiments show how communities may assemble by facilitating one another in harsh, sterile environments, but that arriving after community members have co-evolved can limit invasion success.

microbiology↗