Biological Principles Research Articles

Functional predictability of universal gene circuits in diverse microbial hosts

AbstractAlthough the principles of synthetic biology were initially established in model bacteria, microbial producers, extremophiles and gut microbes have now emerged as valuable prokaryotic chassis for biological engineering. Extending the host range in which designed circuits can function reliably and predictably presents a major challenge for the concept of synthetic biology to materialize. In this work, we systematically characterized the cross‐species universality of two transcriptional regulatory modules—the T7 RNA polymerase activator module and the repressors module—in three non‐model microbes. We found striking linear relationships in circuit activities among different organisms for both modules. Parametrized model fitting revealed host non‐specific parameters defining the universality of both modules. Lastly, a genetic NOT gate and a band‐pass filter circuit were constructed from these modules and tested in non‐model organisms. Combined models employing host non‐specific parameters were successful in quantitatively predicting circuit behaviors, underscoring the potential of universal biological parts and predictive modeling in synthetic bioengineering.

Microplastics, physical-chemical and biological principles of this environmental liability

The advent of plastic to the social situation has suppressed a series of demands from both the industry and the population, due to cost, durability and disposal. Because they can be rigid, malleable, opaque, translucent, easy or difficult to melt by the action of fire, some make them capable of serving as raw material for various products on the market, including those widely used in the food industry. In view of the above, the present study aims at a bibliographical review on the topic of microplastics, where the search will be to verify the primary and secondary steps necessary for the formation of the compound, its direct and indirect influence on food production, the physical-chemical processes through which compounds are obtained and the presence or absence of regulation regarding this environmental liability. The present study aims to analyze as a basis the search for knowledge of the primary and secondary formation of microplastics. Subsequently, together with its main objective, this study aims to search for the physico-chemical and thermodynamic phenomena involved in the process of formation and obtaining of microplastics, the polluting potential and, like all waste, its implications for human health. A study horizon was established covering the years 2015 to 2023, where 3,750 articles were found and after applying open access filters, duplication of publication, words present only in the abstract and not in the text, 49 articles remained that are the object of this study. The direct implications of microplastic pollution are already a relevant reason for discussion and subsequent regulation by managers, researchers, international organizations and society in general. Public health problems that can transform into microplastics, containment and adsorption mechanisms of these compounds in living organisms, are points to be pursued by academia as a whole. Contamination by these compounds was found in bottled mineral water, human milk, processed foods, seafood, showing the extent of contamination of this material.

Hybrid algorithm for global optimization based on periodic selection scheme in engineering computation

PurposeMetaheuristic algorithms based on biology, evolutionary theory and physical principles, have been widely developed for complex global optimization. This paper aims to present a new hybrid optimization algorithm that combines the characteristics of biogeography-based optimization (BBO), invasive weed optimization (IWO) and genetic algorithms (GAs).Design/methodology/approachThe significant difference between the new algorithm and original optimizers is a periodic selection scheme for offspring. The selection criterion is a function of cyclic discharge and the fitness of populations. It differs from traditional optimization methods where the elite always gains advantages. With this method, fitter populations may still be rejected, while poorer ones might be likely retained. The selection scheme is applied to help escape from local optima and maintain solution diversity.FindingsThe efficiency of the proposed method is tested on 13 high-dimensional, nonlinear benchmark functions and a homogenous slope stability problem. The results of the benchmark function show that the new method performs well in terms of accuracy and solution diversity. The algorithm converges with a magnitude of 10-4, compared to 102 in BBO and 10-2 in IWO. In the slope stability problem, the safety factor acquired by the analogy of slope erosion (ASE) is closer to the recommended value.Originality/valueThis paper introduces a periodic selection strategy and constructs a hybrid optimizer, which enhances the global exploration capacity of metaheuristic algorithms.

Glial Regulation of Circuit Wiring, Firing, and Expiring in the Drosophila Central Nervous System.

Molecular genetic approaches in small model organisms like Drosophila have helped to elucidate fundamental principles of neuronal cell biology. Much less is understood about glial cells, although interest in using invertebrate preparations to define their in vivo functions has increased significantly in recent years. This review focuses on our current understanding of the three major neuron-associated glial cell types found in the Drosophila central nervous system (CNS)-astrocytes, cortex glia, and ensheathing glia. Together, these cells act like mammalian astrocytes and microglia; they associate closely with neurons including surrounding neuronal cell bodies and proximal neurites, regulate synapses, and engulf neuronal debris. Exciting recent work has shown critical roles for these CNS glial cells in neural circuit formation, function, plasticity, and pathology. As we gain a more firm molecular and cellular understanding of how Drosophila CNS glial cells interact with neurons, it is clear that they share significant molecular and functional attributes with mammalian glia and will serve as an excellent platform for mechanistic studies of glial function.

Enhancing MANET Performance: A Novel Approach Through Nature-Inspired Scheduling Algorithms

In the rapidly evolving landscape of Mobile Ad Hoc Networks (MANETs), the quest for optimal performance through efficient scheduling remains paramount. This paper, titled "Enhancing MANET Performance: A Novel Approach Through Nature-Inspired Scheduling Algorithms," introduces an innovative methodology that leverages the intricate mechanisms of nature to address the complex challenges inherent in MANET scheduling. Drawing inspiration from the adaptive behaviors observed in natural systems, we have developed a suite of nature-inspired algorithms—encompassing the genetic algorithm, particle swarm optimization, and ant colony optimization—tailored specifically to enhance the scheduling efficiency within the dynamic and decentralized context of MANETs.
 Our research undertakes a comprehensive evaluation of these algorithms against traditional scheduling methods, showcasing a notable improvement in key performance metrics such as network throughput, latency, and energy consumption. The novel contribution of this study lies in the adaptation and optimization of these bio-inspired algorithms for the unique demands of MANET scheduling, culminating in the development of a proprietary analytical model that significantly outperforms existing strategies. Through a rigorous comparative analysis, our results illuminate the superiority of our approach, demonstrating not only enhanced network efficiency but also improved scalability and reliability under varying conditions.
 The implications of this research extend beyond the immediate enhancements to MANET performance, proposing a paradigm shift in how scheduling challenges are approached within ad hoc networks. By bridging the gap between biological principles and technological applications, this study paves the way for future innovations in network management, offering a blueprint for the development of more adaptive, robust, and efficient networking solutions.

A computational model of Alzheimer's disease at the nano, micro, and macroscales.

Mathematical models play a crucial role in investigating complex biological systems, enabling a comprehensive understanding of interactions among various components and facilitating in silico testing of intervention strategies. Alzheimer's disease (AD) is characterized by multifactorial causes and intricate interactions among biological entities, necessitating a personalized approach due to the lack of effective treatments. Therefore, mathematical models offer promise as indispensable tools in combating AD. However, existing models in this emerging field often suffer from limitations such as inadequate validation or a narrow focus on single proteins or pathways. In this paper, we present a multiscale mathematical model that describes the progression of AD through a system of 19 ordinary differential equations. The equations describe the evolution of proteins (nanoscale), cell populations (microscale), and organ-level structures (macroscale) over a 50-year lifespan, as they relate to amyloid and tau accumulation, inflammation, and neuronal death. Distinguishing our model is a robust foundation in biological principles, ensuring improved justification for the included equations, and rigorous parameter justification derived from published experimental literature. This model represents an essential initial step toward constructing a predictive framework, which holds significant potential for identifying effective therapeutic targets in the fight against AD.

Abstract 1248: The BRD8/p53 epigenetic switch re-establishes tumor suppression in glioblastoma

Abstract Glioblastoma (GBM) is the most common and deadly adult primary brain malignancy. Median survival is just 12-14 months, with only about 5% of GBM patients surviving 5 years after diagnosis. This picture has not substantially improved over decades and there is an urgent need to discover more specific and effective treatments for this deadly malignancy. We discovered the bromodomain-containing chromatin regulator BRD8 as essential to GBM lacking p53 mutations (TP53WT), which make up ~71% of cases (1). BRD8 maintains malignancy by crippling p53-mediated tumor suppression in a way distinct from previously described mechanisms: it reprograms the p53 network through the EP400 histone acetyltransferase complex and by bromodomain-directed occupancy of the histone variant H2AZ at p53-induced targets, enforcing a repressive chromatin state that prevents p53-mediated transactivation. Importantly, targeting BRD8 in TP53WT GBM remodels chromatin by evicting H2AZ and enhancing chromatin accessibility, enabling p53 to bind and transactivate its targets. This chromatin remodeling cascade (referred to as the “BRD8/p53 epigenetic switch”) re-establishes p53 activity in TP53WT GBM, normalizing gene expression, evoking cell cycle arrest, inhibiting gliomagenesis, and prolonging survival in xenograft models of TP53WT GBM. Our recent work: (i) reveals that BRD8 opposes p53 function in non-malignant brain cells; (ii) shows that the bromodomain of BRD8 is unique amongst the bromodomain-containing protein family, as it is the only one that selectively reprograms the p53 network; and (iii) demonstrates that targeting BRD8 works synergistically with MDM2 inhibition. Our findings present a previously unappreciated mechanism by which cancer cells side-step p53, indicate that targeting BRD8 re-establishes p53-mediated tumor suppression in TP53WT GBM, highlight unique features of the bromodomain of BRD8, and propose therapies using co-inhibition of BRD8 and MDM2 as a dual-level tactic for boosting up p53. Thus, our work sheds light on new principles of chromatin biology and offers new promise for treating patients with this devastating malignancy. (1)Sun et al., 2023 Nature 613 (7942):195-202. Citation Format: Xueqin Sherine Sun, Alea A. Mills. The BRD8/p53 epigenetic switch re-establishes tumor suppression in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1248.

Evolution and genetics of accessory gland transcriptome divergence between Drosophila melanogaster and D. simulans.

Studies of allele-specific expression in interspecific hybrids have provided important insights into gene-regulatory divergence and hybrid incompatibilities. Many such investigations in Drosophila have used transcriptome data from complex mixtures of many tissues or from gonads, however, regulatory divergence may vary widely among species, sexes, and tissues. Thus, we lack sufficiently broad sampling to be confident about the general biological principles of regulatory divergence. Here, we seek to fill some of these gaps in the literature by characterizing regulatory evolution and hybrid misexpression in a somatic male sex organ, the accessory gland, in F1 hybrids between Drosophila melanogaster and D. simulans. The accessory gland produces seminal fluid proteins, which play an important role in male and female fertility and may be subject to adaptive divergence due to male-male or male-female interactions. We find that trans differences are relatively more abundant than cis, in contrast to most of the interspecific hybrid literature, though large effect-size trans differences are rare. Seminal fluid protein genes have significantly elevated levels of expression divergence and tend to be regulated through both cis and trans divergence. We find limited misexpression (over- or underexpression relative to both parents) in this organ compared to most other Drosophila studies. As in previous studies, male-biased genes are overrepresented among misexpressed genes and are much more likely to be underexpressed. ATAC-Seq data show that chromatin accessibility is correlated with expression differences among species and hybrid allele-specific expression. This work identifies unique regulatory evolution and hybrid misexpression properties of the accessory gland and suggests the importance of tissue-specific allele-specific expression studies.

Characterization of the Pristionchus pacificus "epigenetic toolkit" reveals the evolutionary loss of the histone methyltransferase complex PRC2.

Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation-or lack thereof-of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the "epigenetic toolkit" available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with Caenorhabditis elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to compare with C. elegans. This inventory will enable reverse-genetic experiments related to plasticity and has revealed the first loss of PRC2 in a multicellular organism.

Enhancing stance robustness and jump height in bipedal muscle-actuated systems: a bioinspired morphological development approach.

Recognizing humans' unmatched robustness, adaptability, and learning abilities across anthropomorphic movements compared to robots, we find inspiration in the simultaneous development of both morphology and cognition observed in humans. We utilize optimal control principles to train a muscle-actuated human model for both balance and squat jump tasks in simulation. Morphological development is introduced through abrupt transitions from a 4 year-old to a 12 year-old morphology, ultimately shifting to an adult morphology. We create two versions of the 4 year-old and 12 year-old models- one emulating human ontogenetic development and another uniformly scaling segment lengths and related parameters. Our results show that both morphological development strategies outperform the non-development path, showcasing enhanced robustness to perturbations in the balance task and increased jump height in the squat jump task. Our findings challenge existing research as they reveal that starting with initial robot designs that do not inherently facilitate learning and incorporating abrupt changes in their morphology can still lead to improved results, provided these morphological adaptations draw inspiration from biological principles.

A universal molecular control for DNA, mRNA and protein expression

The expression of genes encompasses their transcription into mRNA followed by translation into protein. In recent years, next-generation sequencing and mass spectrometry methods have profiled DNA, RNA and protein abundance in cells. However, there are currently no reference standards that are compatible across these genomic, transcriptomic and proteomic methods, and provide an integrated measure of gene expression. Here, we use synthetic biology principles to engineer a multi-omics control, termed pREF, that can act as a universal molecular standard for next-generation sequencing and mass spectrometry methods. The pREF sequence encodes 21 synthetic genes that can be in vitro transcribed into spike-in mRNA controls, and in vitro translated to generate matched protein controls. The synthetic genes provide qualitative controls that can measure sensitivity and quantitative accuracy of DNA, RNA and peptide detection. We demonstrate the use of pREF in metagenome DNA sequencing and RNA sequencing experiments and evaluate the quantification of proteins using mass spectrometry. Unlike previous spike-in controls, pREF can be independently propagated and the synthetic mRNA and protein controls can be sustainably prepared by recipient laboratories using common molecular biology techniques. Together, this provides a universal synthetic standard able to integrate genomic, transcriptomic and proteomic methods.

Life and fate of Ervin Bauer (1890–1938), the eminent scholar and foundational theoretical biologist

Ervin Bauer (1890–1938) was the first to build a general molecular-based biological theory. He defined the basic principles of theoretical biology from a thermodynamic perspective, focusing on the capacity of biological systems to produce and support the state of sustainable non-equilibrium. His central work “Theoretical Biology” (1935) was written long before modern advances in molecular biology, genetics, and information theory. Ervin Bauer and his wife Stefánia were executed in Stalin's Great Terror. This paper presents a brief introduction to Ervin Bauer's life and includes his short biography.

Metabolic regulation of the host-fungus interaction: from biological principles to therapeutic opportunities.

Fungal infections present a significant global public health concern, impacting over 1 billion individuals worldwide and resulting in more than 3 million deaths annually. Despite considerable progress in recent years, the management of fungal infections remains challenging. The limited development of novel diagnostic and therapeutic approaches is largely attributed to our incomplete understanding of the pathogenetic mechanisms involved in these diseases. Recent research has highlighted the pivotal role of cellular metabolism in regulating the interaction between fungi and their hosts. In response to fungal infection, immune cells undergo complex metabolic adjustments to meet the energy demands necessary for an effective immune response. A comprehensive understanding of the metabolic circuits governing antifungal immunity, combined with the integration of individual host traits, holds the potential to inform novel medical interventions for fungal infections. This review explores recent insights into the immunometabolic regulation of host-fungal interactions and the infection outcome and discusses how the metabolic repurposing of immune cell function could be exploited in innovative and personalized therapeutic approaches.

The epoch-making importance of Ervin Bauer's theoretical biology

Ervin Bauer was the only biologist who recognized that the best way to develop theoretical biology on an equal footing with theoretical physics was to follow the method that has ensured the great successes of modern theoretical physics: the general method of science. Following this method, he succeeded to find the universal principle of biology. From this principle he managed to derive all the basic equations of biology, that of metabolism, reproduction, growth, responsiveness and successfully explained all the fundamental phenomena of life. In this paper, I introduce Bauer's theoretical biology and discuss whether he understood it within the framework of the modern physical worldview, or in a broader framework. I point out that the theoretical biology of Ervin Bauer is the first to go beyond the physical worldview, to establish a deeper, biological worldview, and thus to represent a major advance in our understanding of the nature of life, with a significance even greater than that of the Copernican turn. Clarifying the difference between the living and the non-living, it is important to consider the difference between machines and living organisms. It is well known that machines are the manifestations of a dual control; globally, their behavior is controlled by their given structure, while locally, their behavior is governed by the physical laws. Based on Bauer's theoretical biology, it is pointed out that living organisms manifest a three-level causality; the ‘additional’, biological level corresponds to the autonomous, time-dependent control of their structures.

Energy-saving robust control of active suspension system based on bioinspired reference model

This paper proposes an energy-saving robust tracking control method for active suspension systems with a bio-inspired reference model and nonlinear extended state observer (NLESO). According to the principle of cheetah running biology, a bionic structure with nonlinear quasi-zero stiffness is designed, which also has ideal Sky-hook damping and vibration-absorbing mass. An NLESO is designed to estimate the total uncertain disturbance and the state of sprung mass in the suspension system, and then an energy-saving robust tracking controller is proposed. The controller consumes less control energy while isolating the vibration of the sprung mass, thus improving the riding comfort of vehicles and saving energy. The simulation results show that, compared with the reference control method, the vertical acceleration of the sprung mass is reduced by 80.68% and 92.42% respectively in the class C road and bump road conditions and the control energy is decreased by 31.71% and 30.50%, respectively. The control effect of the proposed controller for the active suspension system is verified.

Teaching the principles of least-cost poultry feed formulation utilizing the Solver function within a computer software workbook

A Microsoft Excel workbook, User-Friendly Feed Formulation with Data from Australia (UffdAu.xlsm), has been developed for teaching feed formulation techniques to tertiary level, university students. It runs under both Microsoft Windows and Apple iOS operating systems. The example ingredient composition matrix is based on the Australian Feed Ingredient Database to illustrate the biological and econometric principles of least-cost feed formulation. The nutrient data are based roughly on recent primary breeder company recommendations. The workbook is easily adapted to appropriate ingredients, nutrients, and prices most relevant to the students, wherever it is used. The workbook uses the linear routines of Excel's Solver add-in under the Data heading in the header Ribbon. There is a worksheet illustrating how to adapt non-linear responses such as exogenous enzymes to typical linear models using a step function. Additional worksheets illustrate how proximate analysis can be interpreted in modern analytical chemistry terms and, how various feed energy measures are related to feed composition. UffdAu.xlsm is available free of charge from the Poultry Hub Australia website (https://www.poultryhub.org).

SLoN: a spiking looming perception network exploiting neural encoding and processing in ON/OFF channels.

Looming perception, the ability to sense approaching objects, is crucial for the survival of humans and animals. After hundreds of millions of years of evolutionary development, biological entities have evolved efficient and robust looming perception visual systems. However, current artificial vision systems fall short of such capabilities. In this study, we propose a novel spiking neural network for looming perception that mimics biological vision to communicate motion information through action potentials or spikes, providing a more realistic approach than previous artificial neural networks based on sum-then-activate operations. The proposed spiking looming perception network (SLoN) comprises three core components. Neural encoding, known as phase coding, transforms video signals into spike trains, introducing the concept of phase delay to depict the spatial-temporal competition between phasic excitatory and inhibitory signals shaping looming selectivity. To align with biological substrates where visual signals are bifurcated into parallel ON/OFF channels encoding brightness increments and decrements separately to achieve specific selectivity to ON/OFF-contrast stimuli, we implement eccentric down-sampling at the entrance of ON/OFF channels, mimicking the foveal region of the mammalian receptive field with higher acuity to motion, computationally modeled with a leaky integrate-and-fire (LIF) neuronal network. The SLoN model is deliberately tested under various visual collision scenarios, ranging from synthetic to real-world stimuli. A notable achievement is that the SLoN selectively spikes for looming features concealed in visual streams against other categories of movements, including translating, receding, grating, and near misses, demonstrating robust selectivity in line with biological principles. Additionally, the efficacy of the ON/OFF channels, the phase coding with delay, and the eccentric visual processing are further investigated to demonstrate their effectiveness in looming perception. The cornerstone of this study rests upon showcasing a new paradigm for looming perception that is more biologically plausible in light of biological motion perception.

Looking for a Beam of Light to Heal Chronic Pain.

Chronic pain (CP) is a leading cause of disability and a potential factor that affects biological processes, family relationships, and self-esteem of patients. However, the need for treatment of CP is presently unmet. Current methods of pain management involve the use of drugs, but there are different degrees of concerning side effects. At present, the potential mechanisms underlying CP are not completely clear. As research progresses and novel therapeutic approaches are developed, the shortcomings of current pain treatment methods may be overcome. In this review, we discuss the retinal photoreceptors and brain regions associated with photoanalgesia, as well as the targets involved in photoanalgesia, shedding light on its potential underlying mechanisms. Our aim is to provide a foundation to understand the mechanisms underlying CP and develop light as a novel analgesic treatment has its biological regulation principle for CP. This approach may provide an opportunity to drive the field towards future translational, clinical studies and support pain drug development.

Efficacy of 3D Printed Finger Prosthesis for patients affected with Hansen’s Disease to Restore Hand Function

Introduction The greek word LEPROSY was renamed by the term Hansen’s disease by Norwegian physician Gerhard Armauer Hansen. In 2009, WHO Goodwill Ambassador Yohei Sasakawa called for an end to usage of the word leprosy, since he described it as ‘an extremely damaging term’ that contributes to stigma and impacts human rights. Since 2010, leprosy mission gives assurance that the word is not condoned by media channels or used by public figures. HD ranges from mild to severe (based on one or more skin areas affected and damage caused to organs).There were 5.2 million people affected by leprosy globally, in 1980 but by 2020 this decreased to fewer than 2,00,000. Leprosy can affect people in many ways. The Cochrane database of systemic reviews , 2019 lists that 30% of people affected with leprosy experience nerve damage. People with untreated leprosy become visibly disfigured often have psychologic and social problems. Mosby’s Medical Dictionary 2009 defines trophic ulcers as “a pressure ulcer caused by external trauma to a part of body or by vascular insufficiency leading to loss of afferent nerve fibres. The most severe complications result from infection of the peripheral nerves, which causes deterioration of sense of touch and inability to feel pain and temperature. The nerve damage is reversible when treated early, but becomes permanent when appropriate treatment is not available for sufferer. Damage to nerves may cause loss of muscle function, leading to paralysis. It may also lead to sensation abnormalities or numbness, which may lead to additional infections, ulcerations, and joint deformities. Also, damage to peripheral nerves may cause muscle weakness that can result in deformities. M. leprae attacks nerve endings and destroys the body's ability to feel pain and injury. Without feeling pain, people with leprosy have an increased risk of injuring themselves. In some cases, autoamputation has been reported to affect the tip of fingers. People with peripheral nerve damage may unknowingly burn, cut, or otherwise harm themselves. Infected nerves may enlarge also & this can be palpated. The fingers may be weakened, causing them to curve inward (claw hand). When therapeutic amputation is decided for a patient affected with HD, occupational therapist can suggest preserving as much of hand as possible, to prepare wearing 3D printed prosthesis. 3-D printing is a new rising technology, Objects made in 3D printing range from plastic figurines and mould patterns to steel machine parts and titanium surgical implants. Related to Hansen Disease, It facilitates manufacturing hand parts with irregular and uncommon geometric shapes. Freedom offered by 3D printing techniques has paved the way for the application of new design for best appearances. The advantages of 3D printing could be used to fabricate prosthetic hands based on the biological design principles. The purpose of this study is to assess efficacy of 3-D printed finger prosthesis to manipulate objects & to restore hand function in HD clients.

From Nature to Design: Tailoring Pure Mycelial Materials for the Needs of Tomorrow.

Modern efforts to influence materials science with principles of biology have allowed fungal mycelial materials to take a foothold and develop novel solutions for the circular bioeconomy of tomorrow. However, recent studies have shown that the value of tomorrow's green materials is not determined simply by their environmental viability, but rather by their ability to make the polluting materials of today obsolete. With an inherently strong structure of chitin and β-glucan, the ever-adaptable mycelia of fungi can compete at the highest levels with a litany of materials from leather to polyurethane foam to paper to wood. There are significant efforts to optimize pure mycelial materials (PMMs) through the entire process of species and strain selection, mycelial growth, and fabrication. Indeed, the promising investigations of novel species demonstrate how the diversity of fungi can be leveraged to create uniquely specialized materials. This review aims to highlight PMMs' current trajectory, evaluate the successes in technology, and explore how these new materials can help shape a better tomorrow.