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New models of atherosclerosis and multi-drug therapeutic interventions.

MOTIVATION: Atherosclerosis is amongst the leading causes of death globally. However, it is challenging to study in vivo or in vitro and no detailed, openly-available computational models exist. Clinical studies hint that pharmaceutical therapy may be possible. Here, we develop the first detailed, computational model of atherosclerosis and use it to develop multi-drug therapeutic hypotheses. RESULTS: We assembled a network describing atheroma development from the literature. Maps and mathematical models were produced using the Systems Biology Graphical Notation and Systems Biology Markup Lang…

Advances in bone biology: the osteoclast.

Much has been learned about the cell biology and molecular biology of the osteoclast in the last 5 yr. The osteoclast appears to be derived from CFU-GM, the committed monocyte-granulocyte precursor cell. This cell then differentiates into more committed precursors for the osteoclast. The role of the marrow microenvironment appears to be critical for murine osteoclast formation, although in human systems it appears to be nonessential but acts to enhance osteoclast formation and resorption. The osteoclast has been shown to be a secretory cell capable of producing both stimulators and inhibitors

Hyperbolic matrix factorization improves prediction of drug-target associations.

Past research in computational systems biology has focused more on the development and applications of advanced statistical and numerical optimization techniques and much less on understanding the geometry of the biological space. By representing biological entities as points in a low dimensional Euclidean space, state-of-the-art methods for drug-target interaction (DTI) prediction implicitly assume the flat geometry of the biological space. In contrast, recent theoretical studies suggest that biological systems exhibit tree-like topology with a high degree of clustering. As a consequence, emb…

The view of synthetic biology in the field of ethics: a thematic systematic review.

Synthetic biology is designing and creating biological tools and systems for useful purposes. It uses knowledge from biology, such as biotechnology, molecular biology, biophysics, biochemistry, bioinformatics, and other disciplines, such as engineering, mathematics, computer science, and electrical engineering. It is recognized as both a branch of science and technology. The scope of synthetic biology ranges from modifying existing organisms to gain new properties to creating a living organism from non-living components. Synthetic biology has many applications in important fields such as energ

Protocol for single-cell optimization objective and trade-off inference.

Single-cell optimization objective and trade-off inference (SCOOTI) is a computational framework that integrates bulk and single-cell omics data with genome-scale metabolic modeling to infer metabolic objectives and trade-offs in biological systems. Here, we present a protocol for installing and running SCOOTI, using transcriptomics, proteomics, and metabolomics data to constrain metabolic models. We describe steps to interpret metabolic priorities across different cell states or conditions through clustering, dimensionality reduction, and trade-off analysis.

Artificial intelligence for cell-free systems.

Cell-free systems let researchers carry out biological processes like protein synthesis and metabolism without using living cells. This approach has become increasingly important in synthetic biology because it allows for quick testing of ideas, running many experiments simultaneously, and maintaining tight control over reaction conditions. The main challenge has been figuring out how to optimize these systems, since there are so many variables that interact in unpredictable ways. Artificial intelligence (AI), including machine learning, deep learning, and generative models, has begun to tackl

Advances in tools and strategies for spatiotemporal regulation of gene expression in Caenorhabditis elegans.

Spatiotemporal manipulation of gene expression is essential for dissecting gene function, elucidating developmental processes, and uncovering complex physiological mechanisms. As a model organism, Caenorhabditis elegans has played an important role in basic biology research and provides an ideal experimental system for achieving such precise control. With the development of single-copy transgenesis, CRISPR/Cas9-mediated genome editing, and conditional recombination and inducible systems, the genetic toolkits for spatiotemporal regulation of gene expression, and even at the single-cell-resoluti

Biological trajectories toward universal computation: Transposons and chaperone-assisted folding as models of molecular logic.

The question of whether biological systems implement computation-like processes is central to synthetic biology and theoretical biophysics. This paper proposes a formal conceptual framework in which two well-characterized molecular mechanisms-transposable elements ("jumping genes") and chaperone-mediated protein folding-are modeled as computational systems. We argue that transposons, exemplified by the ONSEN retrotransposon in Arabidopsis thaliana, implement signal-responsive genome state transitions formally analogous to probabilistic finite-state machine computation, with capacity for comput

Beyond cultured cells: Frontiers in in situ structural biology.

Structural biology is no longer confined to isolated macromolecules. Correlative light and electron microscopy workflows at cryogenic temperatures have been developed and optimised in cultured cell systems, opening the door for cellular structural biology. The next frontier is expanding these approaches to primary cells, tissues, biopsies, and patient material. The complexity of these samples means each presents unique challenges. Here, we review recent advances that enable the study of primary cells and complex samples. These examples demonstrate the diversity in available workflows and indic

Biochemistry of Aminoacyl tRNA Synthetase and tRNAs and Their Engineering for Cell-Free and Synthetic Cell Applications.

Cell-free biology is increasingly utilized for engineering biological systems, incorporating novel functionality, and circumventing many of the complications associated with cells. The central dogma describes the information flow in biology consisting of transcription and translation steps to decode genetic information. Aminoacyl tRNA synthetases (AARSs) and tRNAs are key components involved in translation and thus protein synthesis. This review provides information on AARSs and tRNA biochemistry, their role in the translation process, summarizes progress in cell-free engineering of tRNAs and

Mitochondrial-Centered Biological Networks in Metabolic Disease: Toward Precision Mitochondrial Medicine.

Obesity and type 2 diabetes (T2D) are multifactorial metabolic disorders characterized by progressive dysfunction of multiple organs and bio … ce from comparative proteomics, mitochondrial biology, bioenergetics, redox biology, signaling, and systems biology to propose the concept of mitochondrial-centered biological networks (MCBNs), in which mitochondria function as dynamic regulatory hubs coordinating interconnected processes that collectively determine metabolic adaptation and tissue resilience. Bui …

Turning a phage anti-defense weapon into an immunity trigger.

Most bacterial immune systems raise an alarm when they sense a phage. A new study in PLOS Biology shows how type II Panoptes reverses this logic by maintaining a quiet signal and sensing infection through its sudden disappearance.

Translational research models for variant subtype bladder cancers: A comprehensive review of the current landscape.

Bladder cancer remains a leading cause of cancer-related mortality in the United States, with most cases classified as conventional urothelial carcinoma. However, a substantial subset of patients presents with aggressive variant histologies, including sarcomatoid, plasmacytoid, and micropapillary subtypes. These variants are associated with early dissemination, treatment resistance, and limited evidence to guide subtype specific management. Despite their clinical relevance, progress in mechanistic understanding and therapeutic development has been hindered due to rarity, underrepresentation in

Modelling the endocrine pancreas in health and disease.

Diabetes mellitus is a multifactorial disease affecting increasing numbers of patients worldwide. Progression to insulin-dependent diabetes mellitus is characterized by the loss or dysfunction of pancreatic β-cells, but the pathomechanisms underlying β-cell failure in type 1 diabetes mellitus and type 2 diabetes mellitus are still poorly defined. Regeneration of β-cell mass from residual islet cells or replacement by β-like cells derived from stem cells holds great promise to stop or reverse disease progression. However, the development of new treatment options is hampered by our limited under

Systems medicine, personalized health and therapy.

The 7th Santorini Conference was held in Santorini, Greece, and brought together 200 participants from 40 countries in several continents, i … uropean Science Foundation [ESF]). The 3 days of the conference stimulated intensive discussions on systems biology and the influence of omics technologies on personalized health. Sixty speakers were invited or selected from early abstracts and gave presentations on the following topics: From systems biology to systems medicine/pharmacology; Omics/translating pha …

Vitiligo Information Resource database v3.

Vitiligo is a multifaceted autoimmune skin disease characterized by the loss of epidermal melanocytes, yet its molecular basis remains poorly understood. To address the need for a specialized systems biology interface, we present VIRdb v3.0, an integrative database combining curated transcriptomics-based datasets with differentially expressed genes, a protein-protein interaction network highlighting regulatory hubs, and an enriched library of natural compounds and FDA-approved drugs targeting vitiligo-related proteins. The platform supports pathway enrichment, molecular docking, and cross-dise…

Reviewing the molecular mechanisms which increase endometrial cancer (EC) risk in women with polycystic ovarian syndrome (PCOS): time for paradigm shift?

Endometrial cancer (EC) is the commonest gynaecological cancer in North American and European women. Even though it has been shown that wome … erature, on the potential molecular links between PCOS and EC but argues for a paradigm shift, to a systems biology-based approach in future research into the molecular links between PCOS and EC. The potential challenges of a systems biology-based approach are outlined but not considered insurmountable.

Развитие микробиотерапии: роль синтетической биологии в инженерных микробных сообществах для точной медицины.

В последние годы исследования в области микробиотических исследований и синтетической биологии были посвящены изучению новых подходов к микробным манипуляциям в терапевтических целях. Тем не менее, по этому аспекту имеется фрагментированная информация с ключевыми идеями, разбросанными по различным дисциплинам, таким, как молекулярная биология, генетика, биоинженерия и медицина. Цель этого обзора заключается в создании преобразующего потенциала синтетической биологии в плане развития исследований и лечения микробиоме, что имеет значительные последствия для здравоохранения, сельского хозяйства и

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… Furthermore, the integration of systems biology will improve the resilience of synthetic pathways, while enhanced biosafety features, such as built-in kill switches, will strengthen containment measures. … Synergies of systems biology and synthetic biology in human microbiome studies. Front. Microbiol. 12, 681982. 10.3389/fmicb.2021.681982 Fisher A. K., Freedman B. G., Bevan D. R., Senger R. S. (2014). …

Modeling of Conjugative- and Phage-Mediated CRISPR-Based System Against Antimicrobial Resistant Bacteria.

OBJECTIVE: Antimicrobial resistance (AMR) poses a significant threat to global health by diminishing the effectiveness of conventional antibiotics. This study aims to assess, using a systems biology approach, a potential synthetic biology-based strategy that employs engineered conjugative probiotic bacteria and bacteriophages to combat AMR, examining the implications of implementing targeted gene silencing as an alternative to direct bacterial killing. METHODS: A comprehensive mathematical model was developed to describe the dynamics of the delivery systems (engineered conjugative probiotic b…

Building Capacity for the Engineering of Biology and Biomanufacturing in Finland.

Finland's efforts on engineering biology (synthetic biology) originate from the investments in genetic engineering at the beginning of 1980s. The efforts were linked early on with industry, such as dairy companies, vaccine production and production of ethanol and industrial enzymes, and development of commercial scale bioprocesses. Timely support for activities in metabolic engineering, systems biology and genome wide technologies (omics) and incorporating bioinformatics and cell level modelling evolved the field naturally towards synthetic biology and biofoundry activities. This foundation ha…