Trends in biotechnology最新文献

Bacterial proteome microarrays are high-throughput, adaptable tools that allow the simultaneous investigation of thousands of proteins from various bacterial species. These arrays are used to explore bacterial pathogenicity, pathogen-host interactions, and clinical diseases. Recent advancements have expanded their application to profiling human antibodies, identifying biomarkers for infectious and autoimmune diseases, and studying antimicrobial peptides (AMPs). This review highlights significant outcomes from recent studies, focusing on their diverse applications in biomedical research. Notable findings include the identification of novel antigens and diagnostic markers for gastrointestinal infections, autoimmune diseases, and mental health disorders. This technology promises to further elucidate the complex relationship between bacteria and their hosts, ultimately informing the development of new diagnostic, therapeutic, and preventive strategies.

Human brain organoids (hBOs) are in vitro, 3D, self-organizing brain tissue structures increasingly used for modeling brain development and disease. Although they traditionally lack vasculature, recent bioengineering developments enable their vascularization, which partly recapitulates neurodevelopmental processes such as neural tube angiogenesis, formation of neurovascular unit (NVU)-like structures, and early barriergenesis. Although vascularized hBOs (vhBOs) are already used to model (defects in) neurovascular development, vascularization efficiency and other outcomes differ substantially between vascularization protocols and overall shortcomings should be considered. For instance, vessel-like structures in vhBOs do not contain blood-like flow nor do they form a functional blood-brain barrier (BBB). Extended characterization, standardization, and the development of new bioengineering techniques may enable broader applications of vhBOs such as drug transport studies.

The demand for diverse nucleic acid delivery vectors, driven by recent biotechnological breakthroughs, offers opportunities for continuous improvements in efficiency, safety, and delivery capacity. With their enhanced safety and substantial cargo capacity, bacterial vectors offer significant potential across a variety of applications. In this review, we explore methods to engineer bacteria for nucleic acid delivery, including strategies such as engineering attenuated strains, lysis circuits, and conjugation machinery. Moreover, we explore pioneering techniques, such as manipulating nanoparticle (NP) coatings and outer membrane vesicles (OMVs), representing the next frontier in bacterial vector engineering. We foresee these advancements in bacteria-mediated nucleic acid delivery, through combining bacterial pathogenesis with engineering biology techniques, as a pivotal step forward in the evolution of nucleic acid delivery technologies.

Engineering and reprogramming cells has significant therapeutic potential to treat a wide range of diseases, by replacing missing or defective proteins, to provide transcription factors (TFs) to reprogram cell phenotypes, or to provide enzymes such as RNA-guided Cas9 derivatives for CRISPR-based cell engineering. While viral vector-mediated gene transfer has played an important role in this field, the use of mRNA avoids safety concerns associated with the integration of DNA into the host cell genome, making mRNA particularly attractive for in vivo applications. Widespread application of mRNA for cell engineering is limited by its instability in the biological environment and challenges involved in the delivery of mRNA to its target site. In this review, we examine challenges that must be overcome to develop effective therapeutics.

In recent decades, the field of synthetic biology has witnessed remarkable progress, driving advances in both research and practical applications. One pivotal area of development involves the design of transgene switches capable of precisely regulating specified outputs and controlling cell behaviors in response to physical cues, which encompass light, magnetic fields, temperature, mechanical forces, ultrasound, and electricity. In this review, we delve into the cutting-edge progress made in the field of physically controlled protein expression in engineered mammalian cells, exploring the diverse genetic tools and synthetic strategies available for engineering targeting cells to sense these physical cues and generate the desired outputs accordingly. We discuss the precision and efficiency limitations inherent in these tools, while also highlighting their immense potential for therapeutic applications.

Encrypted peptides (EPs) have been recently described as a new class of antimicrobial molecules. They have been found in numerous organisms and have been proposed to have a role in host immunity and as alternatives to conventional antibiotics. Intriguingly, many of these EPs are found embedded in proteins unrelated to the immune system, suggesting that immunological responses extend beyond traditional host immunity proteins. To test this idea, we synthesized and analyzed representative peptides derived from non-immune human proteins for their ability to exert antimicrobial and immunomodulatory properties. Most of the tested peptides from non-immune proteins, derived from structural proteins as well as proteins from the nervous and visual systems, displayed potent in vitro antimicrobial activity. These molecules killed bacterial pathogens by targeting their membrane, and those originating from the same region of the body exhibited synergistic effects when combined. Beyond their antimicrobial properties, nearly 90% of the peptides tested exhibited immunomodulatory effects, modulating inflammatory mediators, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). Moreover, eight of the peptides identified, collagenin-3 and 4, zipperin-1 and 2, and immunosin-2, 3, 12, and 13, displayed anti-infective efficacy in two different preclinical mouse models, reducing bacterial infections by up to four orders of magnitude. Altogether, our results support the hypothesis that peptides from non-immune proteins may have a role in host immunity. These results potentially expand our notion of the immune system to include previously unrecognized proteins and peptides that may be activated upon infection to confer protection to the host.

Development of efficient microbial strains for biomanufacturing requires deep understanding of the biology and functional components responsible for the synthesis, transport, and tolerance of the target compounds. A high-quality controllable gene overexpression strain collection was constructed for the industrial workhorse Corynebacterium glutamicum covering 99.7% of its genes. The collection was then used for comprehensive screening of components relevant to biomanufacturing features. In total, 15 components endowing cells with improved hyperosmotic tolerance and l-lysine productivity were identified, including novel transcriptional factors and DNA repair proteins. Systematic interrogation of a subset of the collection revealed efficient and specific exporters functioning in both C. glutamicum and Escherichia coli. Application of the new exporters was showcased to construct a strain with the highest l-threonine production level reported for C. glutamicum (75.1 g/l and 1.5 g/l·h) thus far. The genome-scale gene overexpression collection will serve as a valuable resource for fundamental biological studies and for developing industrial microorganisms for producing amino acids and other biochemicals.

Biotechnology holds the potential to drive innovations across various fields from agriculture to medicine. However, despite numerous interventions, biotechnology education remains highly unequal worldwide. Historically, the high costs and potential exposure to hazardous materials have hindered biotechnology education. Integration of cloud technologies into classrooms has emerged as an alternative solution that is already enabling biotechnology experiments to reach thousands of students globally. We describe several innovations that collectively facilitate real-time experimentation in biotechnology education in remote locations. These advances enable remote access to scientific data and live experiments, promote collaborative research, and ensure educational inclusivity. We propose cloud-enabled live-cell biotechnology as a mechanism for reducing inequalities in biotechnology education and promoting sustainable development.

The integration of nucleic acid amplification (NAA) with the CRISPR detection system has led to significant advancements and opportunities for development in molecular diagnostics. Nevertheless, the incompatibility between CRISPR cleavage and NAA has significantly impeded the commercialization of this technology. Currently, several one-pot detection strategies based on CRISPR systems have been devised to address concerns regarding aerosol contamination risk and operational complexity associated with step-by-step detection as well as the sensitivity limitation of conventional one-pot methods. In this review, we provide a comprehensive introduction and outlook of the various solutions of the one-pot CRISPR assay for practitioners who are committed to developing better CRISPR nucleic acid detection technologies to promote the progress of molecular diagnostics.

Mangroves are impacted by multiple environmental stressors, including sea level rise, erosion, and plastic pollution. Thus, mangrove soil may be an excellent source of as yet unknown plastic-transforming microorganisms. Here, we assess the impact of polyethylene terephthalate (PET) particles and seawater intrusion on the mangrove soil microbiome and report an enrichment culture experiment to artificially select PET-transforming microbial consortia. The analysis of metagenome-assembled genomes of two bacterial consortia revealed that PET catabolism can be performed by multiple taxa, of which particular species harbored putative novel PET-active hydrolases. A key member of these consortia (Mangrovimarina plasticivorans gen. nov., sp. nov.) was found to contain two genes encoding monohydroxyethyl terephthalate hydrolases. This study provides insights into the development of strategies for harnessing soil microbiomes, thereby advancing our understanding of the ecology and enzymology involved in microbial-mediated PET transformations in marine-associated systems.