What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering paths to succeed? Is it possible to create stable, diverse synthetic ecosystems capable of persisting in closed environments? Can synthetic communities be created to thrive on planets different from ours? These and other questions pervade major future developments within synthetic biology. The goal of engineering ecosystems is plagued with all kinds of technological, scientific and ethic problems. In this paper, we consider the requirements for terraformation, i.e., for changing a given environment to make it hospitable to some given class of life forms. Although the standard use of this term involved strategies for planetary terraformation, it has been recently suggested that this approach could be applied to a very different context: ecological communities within our own planet. As discussed here, this includes multiple scales, from the gut microbiome to the entire biosphere.

Fatty acid synthase (FASN)-catalyzed endogenous lipogenesis is a hallmark of cancer metabolism. However, whether FASN is an intrinsic mechanism of tumor cell defense against T cell immunity remains unexplored. To test this hypothesis, here we combined bioinformatic analysis of the FASN-related immune cell landscape, real-time assessment of cell-based immunotherapy efficacy in CRISPR/Cas9-based FASN gene knockout (FASN KO) cell models, and mathematical and mechanistic evaluation of FASN-driven immunoresistance. FASN expression negatively correlates with infiltrating immune cells associated with cancer suppression, cytolytic activity signatures, and HLA-I expression. Cancer cells engineered to carry a loss-of-function mutation in FASN exhibit an enhanced cytolytic response and an accelerated extinction kinetics upon interaction with cytokine-activated T cells. Depletion of FASN results in reduced carrying capacity, accompanied by the suppression of mitochondrial OXPHOS and strong downregulation of electron transport chain complexes. Targeted FASN depletion primes cancer cells for mitochondrial apoptosis as it synergizes with BCL-2/BCL-X_L-targeting BH3 mimetics to render cancer cells more susceptible to T-cell-mediated killing. FASN depletion prevents adaptive induction of PD-L1 in response to interferon-gamma and reduces constitutive overexpression of PD-L1 by abolishing PD-L1 post-translational palmitoylation. FASN is a novel tumor cell-intrinsic metabolic checkpoint that restricts T cell immunity and may be exploited to improve the efficacy of T cell-based immunotherapy.

Quasispecies theory revolutionized our understanding of viral evolution by describing viruses as dynamic populations of genetically diverse variants constantly adapting. This article explores the theory’s role in virus-host interactions, including immune evasion, drug resistance, and viral emergence. We review the original model, recent advances, and key virus dynamics needing incorporation into quasispecies theory. We introduce the ultracube concept as a more realistic multidimensional sequence space to investigate virus evolutionary dynamics.

Semiarid ecosystems (including arid, semiarid and dry-subhumid ecosystems) span more than 40% of extant habitats and contain a similar percentage of the human population. Theoretical models and palaeoclimatic data predict a grim future, with rapid shifts towards a desert state, with accelerated diversity losses and ecological collapses. These shifts are a consequence of the special nonlinearities resulting from ecological facilitation. Here, we investigate a simple model of semiarid ecosystems identifying the so-called ghost, which appears after a catastrophic transition from a vegetated to a desert state once a critical rate of soil degradation is overcome. The ghost involves a slowdown of transients towards the desert state, making the ecosystem seem stable even though vegetation extinction is inevitable. We use this model to show how to exploit the ecological ghosts to avoid collapse. Doing so involves the restoration of small fractions of desert areas with vegetation capable of maintaining a stable community once the catastrophic shift condition has been achieved. This intervention method is successfully tested under the presence of demographic stochastic fluctuations.

Ecosystems are complex systems, currently experiencing several threats associated with global warming, intensive exploitation and human-driven habitat degradation. Because of a general presence of multiple stable states, including states involving population extinction, and due to the intrinsic nonlinearities associated with feedback loops, collapse in ecosystems could occur in a catastrophic manner. It has been recently suggested that a potential path to prevent or modify the outcome of these transitions would involve designing synthetic organisms and synthetic ecological interactions that could push these endangered systems out of the critical boundaries. In this paper, we investigate the dynamics of the simplest mathematical models associated with four classes of ecological engineering designs, named Terraformation motifs (TMs). These TMs put in a nutshell different ecological strategies. In this context, some fundamental types of bifurcations pervade the systems’ dynamics. Mutualistic interactions can enhance persistence of the systems by means of saddle-node bifurcations. The models without cooperative interactions show that ecosystems achieve restoration through transcritical bifurcations. Thus, our analysis of the models allows us to define the stability conditions and parameter domains where these TMs must work.