Yeast has been a robust platform to manufacture a broad range of biofuels, commodity chemicals, natural products and pharmaceuticals. The membrane-bound organelles in yeast provide us the means to access the specialized metabolism for various biosynthetic applications. The separation and compartmentalization of genetic and metabolic events presents us the opportunity to precisely control and program

A growing number of gene delivery strategies are being employed for immunoengineering in applications ranging from infectious disease prevention to cancer therapy. Viral vectors tend to have high gene transfer capability but may be hampered by complications related to their intrinsic immunogenicity. Non-viral methods of gene delivery, including polymeric, lipid-based, and inorganic nanoparticles as

Bacterial Microcompartments (BMCs) are used by diverse bacteria to compartmentalize enzymatic reactions, functioning analogously to the organelles of eukaryotes. The bounding membrane and encapsulated components are composed entirely of protein, which makes them ideal targets for modification by genetic engineering. In contrast to viruses, in which generally only one protein forms the capsid, the shells

Syntheses of many commodities that are produced using microorganisms require cofactors such as ATP and NAD(P)H. Thus, optimization of the flux distribution in central carbon metabolism, which plays a key role in cofactor regeneration, is critical for enhancing the production of the target compounds. Since the intracellular and extracellular conditions change over time in the fermentation process, dynamic

Industrial biosynthesis is a very complex process which depends on a range of different factors, from intracellular genes and metabolites, to extracellular culturing conditions and bioreactor engineering. The identification of species that improve the titer of some reaction is akin to the task of finding a needle in a haystack. This review aims to summarize state-of-the-art biosynthesis titer improvement

Environmental cues are essential in defining tumour malignancy, by promoting tumour initiation, progression and metastatic spreading. Stromal cells may metabolically cooperate or compete with cancer cells, playing a mandatory role in defining cancer metabolic plasticity, potentially dictating the final tumour outcome. Assessing shared nutrients between different tumoural or stromal compartments is

Functional nanopores play an essential role in many biotechnological applications such as sensing, or drug delivery. Prominent examples are polymer functionalized ceramic or solid state nanopores. Intensive research efforts led to a discovery of a plethora of polymer functionalized nanopores demonstrating gated molecular transport upon basically all common stimuli. Nevertheless, nature's biological

Advances in synthetic biology and metabolic engineering across the past few decades have enabled the successful production of many novel chemicals. However, bioproduction of such chemicals is often limited by low yield and titer due to disrupted metabolic homeostasis. Finely tuning cellular metabolism to restore robust metabolic functions entails various genetic modifications, which is often not practical

Synthetic biology has been transformative to the treatment of advanced hematological malignancies by chimeric antigen receptor (CAR)-engineered T cells. A range of obstacles are now understood to limit the responses of solid epithelial-derived tumors to CAR therapy. For example, inefficient tumor homing and a fortified stroma can restrain the number of CAR-T cells reaching the tumor bed. Upon transendothelial

Immunomodulation has become a promising and growing field of cancer research. Compelling results from a variety of studies provide strong evidence for the importance of commensal bacteria on oncologic outcomes and response to antitumor immunotherapies. The gut microbiome has emerged as a new prognostic biomarker and a potential therapeutic target to enhance the efficacy of immunotherapy.

Metabolite concentrations, fluxes, and free energies constitute the basis for understanding and controlling metabolism. Mass spectrometry and stable isotopes are integral tools in quantifying these metabolic features. For absolute metabolite concentration and flux measurement, 13C internal standards and tracers have been the gold standard. In contrast, no established methods exist for comprehensive

Microbial systems have been widely studied and exploited through genetic engineering to address industrial needs and societal challenges. However, owing to their complexity, singular approaches often do not yield desired or optimal results, pushing researchers to explore combinatorial strategies. With advances in synthetic biology, various methods can readily be employed to generate large and comprehensive

Yarrowia lipolytica has emerged as an important non-model host for terpene production. However, three main challenges remain in industrial production using this yeast. First, considerable knowledge gaps exist in metabolic flux across multiple compartments, cofactor generation, and catabolism of non-sugar carbon sources. Second, many enzymatic steps in the complex-terpene synthesis pathway can pose

Metabolomics is a rapidly expanding technology that finds increasing application in a variety of fields, form metabolic disorders to cancer, from nutrition and wellness to design and optimization of cell factories. The integration of metabolic snapshots with metabolic fluxes, physiological readouts, metabolic models, and knowledge-informed Artificial Intelligence tools, is required to obtain a system-level

Hydrogen is already a major commodity and process intermediate for fertilizer production, petroleum processing, and chemical synthesis. It also offers unrealized potential for energy storage. While biological production offers an expandable and sustainable source, enthusiasm has been dampened by slow research progress. Also, the very low cost of natural gas (the major current hydrogen source) imposes

Genetic variants are often not predictive of the phenotypic outcome. Individuals carrying the same pathogenic variant, associated with Mendelian or complex disease, can manifest to different extents, from severe-to-mild to no disease. Improving the accuracy of predicted clinical manifestations of genetic variants has emerged as one of the biggest challenges in precision medicine, which can only be

Pseudomonads are well-known to thrive in diverse and complex nutritional habitats, and these capabilities make Pseudomonas species attractive as whole-cell biocatalysts. Industrial bioconversion processes often rely on complex uptake and synergistic metabolic systems due to the presence of varied carbon substrates in nutrient feedstocks. Isotope labeling experiments (ILEs) are emerging techniques used

Generating novel functionality from well characterised synthetic parts and modules lies at the heart of synthetic biology. Ideally, circuitry is rationally designed in silico with quantitatively predictive models to predetermined design specifications. Synthetic circuits are intrinsically stochastic, often dynamically modulated and set in a dynamic fluctuating environment within a living cell. To build

Redox metabolism plays an essential role in the central metabolic network of all living cells, connecting, but at the same time separating, catabolic and anabolic pathways. Redox metabolism is inherently linked to the excretion of overflow metabolites. Overflow metabolism allows for higher substrate uptake rates, potentially outcompeting other microorganisms for the same substrate. Within dynamically

Genetically encodable fluorescent biosensors provide spatiotemporal information on their target analytes in a label-free manner, which has enabled the study of cell biology and signaling in living cells. Over the past three decades, fueled by the development of a wide palette of fluorescent proteins, protein-based fluorescent biosensors against a broad array of targets have been developed. Recently

Patient-derived xenografts (PDXs) are obtained by transplanting fragments of a patient's tumour into immunodeficient mice. Growth and propagation of PDXs allows correlating therapeutic response in vivo with extensive, multi-dimensional molecular annotation, leading to identification of predictive biomarkers. PDXs are increasingly recognised as clinically relevant models of cancer for several reasons

We review recent advances in the design and expression of synthetic RNA sequences inside cells, to regulate gene expression and to achieve spatial localization of components. We focus on approaches that exploit the programmability of the secondary and tertiary structure of RNA to build scalable and modular devices that fold spontaneously and have the capacity to respond to environmental inputs.

Elucidating the mechanistic basis of spore germination and outgrowth remains a difficult challenge with crucial implications in the numerous scientific and engineering disciplines. Omics studies have revealed numerous new biochemical insights and single-spore studies link molecular insights directly with spore heterogeneity behaviors. This field is expected to advance at greater speed with the application

Oleaginous yeasts natively produce surplus triacylglycerol lipid and can be engineered for higher yield and productivity. Most enzymatic steps of triacylglycerol production are characterized, but key parts of the pathway remain unknown. This introduces uncertainty to metabolic engineering strategy and the upper limit of achievable lipid yield. Here, we present our current understanding of the oleaginous

In biomedical applications of machine learning, relevant information often has a rich structure that is not easily encoded as real-valued predictors. Examples of such data include DNA or RNA sequences, gene sets or pathways, gene interaction or coexpression networks, ontologies, and phylogenetic trees. We highlight recent examples of machine learning models that use structure to constrain model architecture

Immune cells are capable of sensing various signals in the microenvironment and turning on specific immune functions in response. The appropriate transition of immune cells into diverse functional states, which is crucial for immunity, involves complex and well-regulated changes in transcriptional program. Accumulating evidence shows that epigenetic remodeling plays a central role in mediating the

Bacteria are widely used for commercially producing biomolecules. However, attempts to rationally design production strains and optimize cultivation conditions are frequently counteracted by the emergence of mutants with reduced production characteristics that decrease overall process yield. The reason why these mutants arise is likely because of a mismatch between the ecological conditions under which

Microbial cells in nature live within dense multispecies conglomerates, forming a self-organizing ecosystem. In such assemblies, genotypes interact with each other in a myriad of ways, driving community dynamics and functionalities. The role of interactions between genotypes and their consequences for spatial structure and functional outcomes are being increasingly studied to understand the ecology

The nematode Caenorhabditis elegans offers unique advantages that enable a comprehensive delineation of the cellular and molecular mechanisms underlying devastating human pathologies such as stroke, ischemia and age-associated neurodegenerative disorders. Genetic models of human diseases that closely simulate several disease-related phenotypes have been established in the worm. These models allow the

Mammalian synthetic gene circuits have promise in biological and medical research due to their capability of controlling cellular functions. Especially, post-transcriptional circuits are growing in interest because of features that include compatibility and superior safety. RNA-based molecular nanodevices are often a core component in these circuits. RNA nanodevices that act as translational controllers

One of the most interesting, difficult, and potentially useful topics in computational biology is the inference of gene regulatory networks (GRNs) from expression data. Although researchers have been working on this topic for more than a decade and much progress has been made, it remains an unsolved problem and even the most sophisticated inference algorithms are far from perfect. In this paper, we