CRISPR-based technique unlocks healing power of mitochondria for heart failure therapy

Mario Escobar
Photo Credit: Jeff Fitlow/Rice University

Scientific Frontline: "At a Glance" Summary: CRISPR-Based Mitochondrial Therapy for Heart Failure

• Main Discovery: Researchers at Rice University and Baylor College of Medicine utilized a nonediting CRISPR technique to safely increase mitochondrial production in heart cells, improving cellular energy levels without causing cellular burnout or malfunction.
• Methodology: The scientific team developed a nonediting CRISPR system that functions as an activation switch. Instead of editing the genome or forcing gene overproduction, the system fine-tunes natural regulatory pathways, specifically targeting the PPARGC1A gene, to prompt human cardiomyocytes to assemble more mitochondria in a measured way.
• Key Data: Heart failure is fundamentally a cellular energy crisis that currently impacts 6.8 million Americans, carrying a high lifetime risk where 1 in 4 adults in the United States are expected to develop the condition.
• Significance: The system successfully improved the rate of oxygen consumption and overall mitochondrial function across various models, including animal models and adult human heart donor tissue from both normal and diseased hearts, addressing the root cause of cardiac energy deficiency.
• Future Application: This approach offers a promising foundation for developing sustainable treatments for heart failure and other metabolic diseases by actively restoring impaired cellular energy supply rather than conventional approaches that merely reduce cardiac energy demand.
• Branch of Science: Molecular Biology, Bioengineering, Cardiology, and Genetics

Just the Right Amount: Microbial Nutrients Drive Success and Failure of Antibiotics

Micrographs show an E. coli population (green) encountering an antibiotic, fosfomycin (initial concentration 2.05 mg/mL, equivalent to 250× MIC), as it diffuses in from the cell-free reservoir on the left. Adding 0.22 mm glucose to the reservoir reveals a propagating front of cell death, indicated by the replacement of green signal from live cells with magenta signal from dead cells.
Image Credit: Anna Hancock, Datta Lab

Scientific Frontline: "At a Glance" Summary: Microbial Nutrients and Antibiotic Efficacy

• Main Discovery: Microbial nutrients dictate the success or failure of antibiotics in structured bacterial communities, creating an observable death front where metabolically active surface cells perish while nutrient-starved interior cells survive.
• Methodology: Researchers immobilized Escherichia coli in a specialized hydrogel mimicking the extracellular matrix and introduced antibiotics and nutrients from an adjacent cell-free reservoir, tracking cellular death and survival in real time via fluorescent signals and optical microscopy.
• Key Data: Application of fosfomycin at 2.05 mg/mL, representing 250 times the standard minimum inhibitory concentration, alongside 0.22 mm glucose generated a propagating death front, whereas the exact antibiotic concentration yielded no cellular death in the absence of nutrients.
• Significance: The findings reveal a long-theorized nutrient bottleneck, explaining why antibiotics that successfully eliminate bacteria in thoroughly mixed laboratory liquid cultures frequently fail to eradicate spatially structured infections within the human body.
• Future Application: The developed mathematical model and experimental platform will serve as a quantitative framework to predict effective antibiotic dosages and design targeted therapeutic strategies that prevent the emergence of antimicrobial resistance.
• Branch of Science: Chemical Engineering, Bioengineering, and Biophysics.
• Additional Detail: Providing excess nutrients to the bacterial population functions as a double-edged sword, unexpectedly promoting the rapid regrowth of heterogeneous, antibiotic-resistant subpopulations in the wake of the initial death front.

Reinforced Enzyme Expression Drives High Production of Durable Lactate-Based Polyester

Lactate-enriched high-molecular-weight LAHB combines practical toughness with biodegradability Image caption: Reinforced expression of the lactate-polymerizing enzyme gene in recombinant bacteria leads to enhanced production of poly[(D-lactate)-co-(R)-3-hydroxybutyrate] (LAHB) with improved toughness and biodegradability.
Image Credit: Professor Seiichi Taguchi from Shinshu University, Japan
(CC BY 4.0)

Scientific Frontline: "At a Glance" Summary: Reinforced Enzyme Expression for High Production of Durable Lactate-Based Polyester

• Main Discovery: Researchers achieved the highest recorded production titer of high-molecular-weight poly[(D-lactate)-co-(R)-3-hydroxybutyrate] (LAHB) by reinforcing the gene expression of a lactate-polymerizing enzyme, successfully balancing mechanical toughness with marine biodegradability.
• Methodology: A lactate-polymerizing enzyme-expressing plasmid vector was introduced into the GS3 series of Cupriavidus necator bacteria using electroporation. The modified GSXd147 strain was then cultured through fed-batch fermentation using glucose as a carbon source, followed by mechanical, thermal, and biodegradability assessments of the purified polymer.
• Key Data: The modified bacterial strain produced 97 g/L dry cell weight comprising 70 wt% LAHB within 48 hours, yielding a record polymer titer of 68 g/L. The resulting material featured a 15.4 mol% lactate fraction, approximately 20 MPa tensile strength, 190% elongation at break, and achieved over 75% biodegradation in natural seawater within five weeks.
• Significance: Overcoming a major enzymatic bottleneck demonstrates that retaining the high molecular weight necessary for structural strength does not compromise the marine biodegradability of the polymer, establishing a highly functional and sustainable alternative to petroleum-based plastics.
• Future Application: This biotechnological approach enables the industrial-scale manufacturing of high-quality, bio-based plastic polymers for commercial packaging and goods, offering a practical solution to directly mitigate the global microplastics crisis.
• Branch of Science: Bioengineering, Biotechnology, and Polymer Chemistry.
• Additional Detail: The collaborative research involving Shinshu University, Kaneka Corporation, and the National Institute of Advanced Industrial Science and Technology will be published in Volume 246 of the journal Polymer Degradation and Stability.

Cancer treatment: optimization of CAR T-cell therapy

LMU physician Sebastian Kobold
Photo Credit: © LMU / Stephan Höck

Scientific Frontline: Extended "At a Glance" Summary

The Core Concept: An advanced form of immunotherapy in which Chimeric Antigen Receptor (CAR) T cells are genetically engineered to resist immunosuppressive signals found within solid tumors, enabling the immune system to effectively destroy cancer cells that were previously resistant to treatment.

Key Distinction/Mechanism: While standard CAR T-cell therapy is highly effective against blood cancers, it often fails against solid tumors because a metabolite called prostaglandin E2 (PGE2) suppresses the T cells' function. This new approach involves removing the specific receptors on the T cells that PGE2 binds to; by eliminating these binding sites, the T cells become "deaf" to the tumor's suppression signal and remain active to attack the malignancy.

Origin/History:

• 2024: Professor Sebastian Kobold’s research group at LMU University Hospital identifies that PGE2 blocks T cells in the tumor vicinity.
• 2026: The team, in cooperation with the University of Tübingen, publishes their success in engineering PGE2-resistant cells in Nature Biomedical Engineering.

Major Frameworks/Components:

• Chimeric Antigen Receptor (CAR) T Cells: Patient-derived immune cells modified to recognize specific cancer proteins (like CD19).
• Prostaglandin E2 (PGE2): An immunosuppressive metabolite in the tumor microenvironment that normally inhibits immune response.
• Receptor Knockout: The genetic removal of PGE2 receptors from T cells to prevent immunosuppression.

Paralysis treatment heals lab-grown human spinal cord organoids

Fluorescent micrographs showing increased neurite outgrowth from a human spinal cord organoid treated with fast-moving “dancing molecules” (left) compared to one treated with slow-moving molecules (right) containing the same bioactive signals
Image Credit: Samuel I. Stupp/Northwestern University

Scientific Frontline: Extended "At a Glance" Summary

The Core Concept: Lab-grown human spinal cord organoids are miniature, three-dimensional tissue models derived from stem cells that mimic the complex structure and function of the human spinal cord to simulate injuries and test regenerative treatments.

Key Distinction/Mechanism: Unlike previous models, these organoids incorporate microglia—the central nervous system's immune cells—allowing researchers to accurately replicate the inflammatory response and glial scarring seen in human spinal cord injuries. The "dancing molecules" therapy creates a nanofiber scaffold where rapidly moving molecules effectively engage cellular receptors to trigger neurite growth and reverse paralysis, a mechanism significantly more effective than therapies using static molecules.

Major Frameworks/Components:

• Induced Pluripotent Stem Cells (iPSCs): The source material for growing the organoids, allowing for patient-specific tissue generation.
• Supramolecular Therapeutic Peptides (STPs): The chemical basis of the "dancing molecules" that assemble into nanofibers.
• Microglia Integration: The inclusion of immune cells to create a "pseudo-organ" that mimics natural inflammatory responses.
• Glial Scarring: A physical barrier to nerve regeneration that the therapy successfully diminished in trials.

Branch of Science: Regenerative Medicine, Nanotechnology, Neuroscience, and Bioengineering.

Future Application: The technology paves the way for personalized medicine, where a patient's own stem cells could be used to grow implantable tissues that avoid immune rejection. It also offers a platform to test treatments for chronic, long-term spinal cord injuries and other neurodegenerative conditions.

Why It Matters: This advancement bridges the gap between animal studies and clinical trials, providing a highly accurate human model for spinal cord injury. It validates a promising therapy that has earned Orphan Drug Designation from the FDA, offering renewed hope for restoring function in paralyzed patients.

Physical pressure on the brain triggers neurons’ self-destruction programming

Anna Wenninger and Maksym Zarodniuk demonstrate a research project in the Patzke Lab.
Photo Credit: Michael Caterina/University of Notre Dame

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Chronic physical compression on the brain, such as that exerted by a growing tumor, triggers specific molecular pathways that program neurons to self-destruct, independent of direct tissue invasion.
• Methodology: Researchers created a model neural network using induced pluripotent stem cells (iPSCs) to mimic the brain's environment, applied mechanical pressure to simulate glioblastoma growth, and analyzed the resulting cellular responses via mRNA sequencing and preclinical live models.
• Key Data: The sequencing revealed a marked increase in HIF-1 molecules and AP-1 gene expression in compressed cells, specific biomarkers indicating stress adaptation and neuroinflammation that precipitate neuronal death and synaptic dysfunction.
• Significance: This study isolates mechanical force as a critical, independent factor in neurodegeneration, explaining why patients with brain tumors often suffer from cognitive decline, motor deficits, and seizures even in non-cancerous brain regions.
• Future Application: Identifying these specific death-signaling pathways provides novel targets for drugs designed to block mechanically induced neuron loss, with potential relevance for treating traumatic brain injury (TBI) alongside brain cancer.
• Branch of Science: Neuroscience, Bioengineering, and Oncology.

The brain uses eye movements to see in 3D

Professor Greg DeAngelis (left) looks on as postdoctoral fellow Vitaly Lerner performs a virtual reality task investigating how eye movements help the brain interpret 3D space.
Photo Credit: University of Rochester / John Schlia

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Visual motion patterns generated by eye movements are actively used by the brain to perceive depth and 3D space, contradicting the long-held belief that this motion is mere "noise" the brain must subtract.
• Methodology: Researchers formulated a theoretical framework predicting human perception during eye movements and validated it using 3D virtual reality tasks where participants estimated the direction and depth of moving objects while maintaining specific focal points.
• Key Data: Experimental results showed participants committed consistent, predictable patterns of errors in depth and motion estimation that aligned precisely with the researchers' theoretical model, confirming the brain processes rather than ignores this visual input.
• Significance: This finding fundamentally shifts the understanding of visual processing by demonstrating that the brain analyzes global image motion patterns to infer eye position relative to the environment and interpret spatial structure.
• Future Application: Findings could enhance Virtual Reality (VR) technology by incorporating eye-movement-relative motion calculations, potentially reducing motion sickness caused by mismatches between displayed images and the brain's expectations.
• Branch of Science: Neuroscience, Visual Science, and Biomedical Engineering.

New tissue models could help researchers develop drugs for liver disease

Researchers created a mini “liver-on-a-chip.” Tiny clusters of liver cells (shown in magenta) are embedded within a network of blood vessels (green). The vessels can carry fluid, shown here with blue dye, allowing scientists to study how liver disease develops.
Image Credit: Erin Tevonian and Ellen Kan
(CC BY-NC-ND 4.0)

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Development of two advanced microfluidic liver tissue models that accurately replicate human liver architecture, including functional blood vessel networks and immune system interactions, to study metabolic diseases.
• Methodology: Researchers modified the "LiverChip" scaffold to support vascular growth and monocyte infiltration, while separately triggering disease states by exposing tissues to elevated levels of glucose, fatty acids, and insulin to mimic metabolic dysfunction.
• Key Data: The study highlighted that metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 100 million Americans; the model demonstrated that the drug resmetirom can induce inflammation, potentially explaining its limited 30% patient efficacy.
• Significance: These platforms provide the first reliable method to observe the interplay between hepatocytes, immune cells, and vasculature in a lab setting, offering a superior alternative to animal models for predicting human drug responses.
• Future Application: Accelerating the identification and safety testing of therapeutics for fatty liver disease (MASLD) and its severe form (MASH), as well as facilitating patient-specific drug screening.
• Branch of Science: Tissue Engineering and Biomedical Engineering.
• Additional Detail: The research confirmed that insulin resistance directly leads to vascular leakiness and increased inflammation markers, key drivers in the progression from early-stage liver disease to fibrosis.

Bubble Bots: Simple Biocompatible Microrobots Autonomously Target Tumors

A scanning electron microscope image of mass-produced microbubbles produced by simply using an ultrasound probe to agitate a BSA solution.
Image Credit: Gao Lab/Caltech

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Development of "bubble bots," biocompatible microrobots comprising protein-shelled gas bubbles that autonomously navigate to tumors for targeted drug delivery.
• Methodology: Scientists use ultrasound to agitate bovine serum albumin into microbubbles, modifying their surfaces with urease for urea-fueled propulsion and catalase to steer toward high hydrogen peroxide concentrations naturally found in tumors.
• Key Data: Trials in mice demonstrated a roughly 60 percent reduction in bladder tumor weight over 21 days compared to standard drug treatments alone.
• Significance: The design eliminates the need for complex fabrication or constant external magnetic guidance, offering a scalable, "smart" solution that autonomously locates pathological sites.
• Future Application: Clinical oncology treatments requiring deep tissue penetration and localized chemotherapy release to minimize systemic side effects.
• Branch of Science: Medical Engineering, Nanotechnology
• Additional Detail: Once at the target site, focused ultrasound is employed to burst the bubbles, generating force that drives the therapeutic cargo deeper into the tumor tissue than passive diffusion allows.

A portable ultrasound sensor may enable earlier detection of breast cancer

The probe, which is a little smaller than a deck of cards, contains an ultrasound array arranged in the shape of an empty square, a configuration that allows the array to take 3D images of the tissue below.
Photo Credit: Conformable Decoders Lab at the MIT Media Lab
(CC BY-NC-ND 4.0)

Scientific Frontline: "At a Glance" Summary

• Main Discovery: MIT researchers developed a fully portable, miniaturized ultrasound system capable of generating real-time 3D images for the early detection of breast cancer.
• Methodology: The device employs a "chirped data acquisition" (cDAQ) architecture with a probe featuring an empty-square transducer array; it rests gently on the skin to capture volumetric data without the tissue compression required by traditional probes.
• Key Data: The processing motherboard costs approximately $300 to manufacture, operates on a standard 5V power supply, and enables the probe (smaller than a deck of cards) to image up to 15 centimeters deep into tissue.
• Significance: This low-power technology addresses the detection gap for "interval cancers"—which account for 20% to 30% of breast cancer cases—by enabling frequent, accessible screening in rural or low-resource settings without the need for heavy hospital equipment.
• Future Application: The team plans to miniaturize the electronics to the size of a fingernail for smartphone integration, develop AI algorithms to guide user placement, and launch a commercial wearable version for at-home monitoring.
• Branch of Science: Biomedical Engineering and Medical Imaging.
• Additional Detail: In initial tests on a 71-year-old subject, the system successfully identified cysts and reconstructed full 3D images without the geometric distortion common in conventional compression-based ultrasound.

Scientists develop first gene-editing treatment for skin conditions

Dr. Sarah Hedtrich (center) and her team examine a skin-on-a-chip model used to test the new CRISPR-based therapy on living human skin samples.
Photo Credit: UBC Faculty of Medicine.

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers developed the first topical CRISPR-based gene therapy capable of correcting disease-causing mutations directly within human skin tissue.
• Methodology: The treatment utilizes lipid nanoparticles (LNPs) to deliver gene-editing machinery into skin stem cells through microscopic, pain-free channels created by a clinically approved laser.
• Key Data: In living human skin models of autosomal recessive congenital ichthyosis (ARCI), the therapy restored up to 30 percent of normal skin function, a level considered clinically meaningful.
• Significance: This breakthrough overcomes the skin's protective barrier to enable localized, potentially permanent genetic correction without the safety risks of systemic off-target effects.
• Future Application: The platform is being adapted for other severe genetic skin diseases like epidermolysis bullosa, as well as common conditions like eczema and psoriasis, with plans for first-in-human clinical trials.
• Branch of Science: Biomedical Engineering, Dermatological Genetics, and Nanomedicine.

Researchers find differences between two causes of heart valve narrowing

UC Irvine’s Arash Kheradvar (left) and Gregg Pressman of Jefferson Health and their teams collaborated on a project to underscore differences in two prevalent forms of mitral valve stenosis in the heart. The research will help improve the diagnosis and treatment of the heart condition that impacts as much as 15 percent of the population.
Photo Credit: Arash Kheradvar / UC Irvine

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers identified fundamental structural and hemodynamic differences between mitral annular calcification (MAC)-related stenosis and rheumatic mitral stenosis, proving they are distinct pathological entities.
• Methodology: Investigators conducted a two-phase study involving 3D transesophageal echocardiography analysis of 70 patients and the creation of patient-specific 3D-printed silicone valve models for testing in a heart flow simulator.
• Key Data: MAC-related stenosis patients exhibited smaller valve volumes, apically displaced hinge points, and higher kinetic energy loss compared to rheumatic patients, despite often possessing a relatively larger geometric orifice area.
• Significance: The findings reveal that current diagnostic standards based on rheumatic disease frequently underestimate the severity of MAC-related obstruction, potentially leading to inadequate clinical decision-making.
• Future Application: This research facilitates the development of disease-specific diagnostic criteria and informs the design of transcatheter and surgical therapies specifically tailored for calcification-driven valve anatomy.
• Branch of Science: Cardiovascular Medicine, Biomedical Engineering, and Radiological Sciences.
• Additional Detail: Mitral annular calcification affects approximately 8 to 15 percent of the general population and serves as a significant marker for broader cardiovascular risks, including stroke and increased mortality.

Tapping the engines of cellular electrochemistry and forces of evolution

Biological condensates are clumps of molecules that condense and scatter apart based on the surrounding chemical and electrical environment in a cell. Recent work from WashU researchers shows how to design and embed these proteins into living systems to serve as electron generators.
Image Credit: AI-generated image courtesy of Dai lab

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers successfully engineered "intrinsically disordered proteins" into biological condensates that function as nanoscale electrochemical "battery droplets" within living cells, capable of generating voltage and driving redox reactions.
• Methodology: The team utilized "directed evolution" in E. coli bacteria, subjecting protein sequences to selective pressures to guide the self-assembly of condensates that create interfacial electric fields similar to electrode-electrolyte boundaries in traditional batteries.
• Key Data: The engineered bio-batteries successfully drove the synthesis of gold and copper nanoparticles directly inside cells and executed redox reactions capable of killing bacteria without the use of traditional antibiotics.
• Significance: This establishes a new framework for "electrogenic protein powerhouses," proving that soft biological matter can store and release electrochemical energy on demand to power synthetic biological signals and reactions.
• Future Application: Applications include sustainable bioproduction, wastewater decontamination (via pollutant degradation), and "biohybrid" medical devices designed to fight infection or reverse antibiotic resistance.
• Branch of Science: Synthetic Biology, Biomedical Engineering, and Electrochemistry.
• Additional Detail: The study overcomes a significant hurdle in evolutionary biology by successfully applying directed evolution to non-structured (disordered) proteins, enabling the programmable design of cellular function based on survival and fitness.

Exploring metabolic noise opens new paths to better biomanufacturing

WashU researchers track single cells to reveal enzyme copy number fluctuation as the main source of metabolic noise.
Image Credits: Alex Schmitz and Xinyue Mu

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Identification of enzyme copy number fluctuation arising from stochastic gene expression as the primary source of metabolic noise in microbial biomanufacturing.
• Methodology: Researchers utilized microfluidic devices to track single Escherichia coli cells engineered to produce betaxanthin (a yellow pigment), measuring both the metabolite and the enzyme concurrently during growth and division, followed by computational modeling and fermentation validation.
• Key Data: Approximately 50% of the observed metabolic noise stems from fluctuations in the production enzyme, while variations in cell growth rate account for less than 10% of the variability; cells were observed switching between high- and low-production states within a few hours.
• Significance: This finding clarifies why microbial productivity often fluctuates or drops in fermentation tanks, enabling the design of gene circuits that link higher enzyme expression to faster growth for sustained high-yield production.
• Future Application: Enhanced biomanufacturing of pharmaceuticals, supplements, biodegradable plastics, and fuels by deploying engineered strains that maintain peak metabolic activity.
• Branch of Science: Bioengineering, Synthetic Biology and Chemical Engineering.
• Additional Detail: This research supports the development of a zero-waste circular economy by improving the reliability of microbial fermentation processes.

Intraoperative Tumor Histology May Enable More-Effective Cancer Surgeries

From left to right: Images of kidney tissue as detected with UV-PAM, as imaged by AI to mimic traditional H&E staining, and as they appear when directly treated with H&E staining.
Image Credit: Courtesy of California Institute of Technology

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers developed ultraviolet photoacoustic microscopy (UV-PAM) integrated with deep learning to perform rapid, label-free, subcellular-resolution histology on excised tumor tissue directly in the operating room.
• Mechanism: A low-energy laser excites the absorption peaks of DNA and RNA nucleic acids to generate ultrasonic vibrations; AI algorithms then process these signals to create virtual images that mimic traditional hematoxylin and eosin (H&E) staining without chemical processing.
• Key Data: The system achieves a spatial resolution of 200 to 300 nanometers and delivers diagnostic results in under 10 minutes (potentially under 5 minutes), effectively identifying the dense, enlarged nuclei characteristic of cancer cells.
• Context: Unlike standard pathology, which requires time-consuming freezing, fixation, and slicing that can damage fatty tissues like breast tissue, this method preserves sample integrity and eliminates preparation artifacts.
• Significance: This technology aims to drastically reduce re-operation rates—currently up to one-third for breast cancer lumpectomies—by allowing surgeons to confirm clean tumor margins intraoperatively across various tissue types (breast, bone, skin, organ).

X-raying auditory ossicles – a new technique reveals structures in record time

Scientists at PSI were able to observe the local collagen structures in an ossicle by scanning it with an X-ray beam. The different colours of the cylinders indicate how strongly the collagen bundles are spatially aligned in a section measuring 20 by 20 by 20 micrometres.
Image Credit: © Paul Scherrer Institute PSI/Christian Appel

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers refined a "tensor tomography" X-ray diffraction technique that simultaneously detects biological structures ranging from nanometers to millimeters, significantly accelerating the imaging process.
• Methodology: The team used a precisely rotated X-ray beam (approx. 20 micrometers wide) to generate millions of interference patterns around two axes, which software then reconstructed into a 3D tomogram.
• Key Statistic: The optimized process reduced the measurement time for a complete tomogram from roughly 24 hours to just over one hour.
• Context: To validate the method, the team imaged the auditory ossicle (anvil) of the ear, successfully mapping the spatial orientation of nanometer-sized collagen fibers crucial for sound transmission.
• Significance: This drastic reduction in scan time makes statistical studies involving hundreds of samples feasible, aiding biomedical research in areas like bone tissue analysis and implant development.

What Is: Organoid

Organoids: The Science and Ethics of Mini-Organs
Image Credit: Scientific Frontline / AI generated

The "At a Glance" Summary

• Defining the Architecture: Unlike traditional cell cultures, organoids are 3D structures grown from pluripotent stem cells (iPSCs) or adult stem cells. They rely on the cells' intrinsic ability to self-organize, creating complex structures that mimic the lineage and spatial arrangement of an in vivo organ.
• The "Avatar" in the Lab: Organoids allow for Personalized Medicine. By growing an organoid from a specific patient's cells, researchers can test drug responses on a "digital twin" of that patient’s tumor or tissue, eliminating the guesswork of trial-and-error prescriptions.
• Bridge to Clinical Trials: Organoids serve as a critical bridge between the Petri dish and human clinical trials, potentially reducing the failure rate of new drugs and decreasing the reliance on animal testing models which often fail to predict human reactions.
• The Ethical Frontier: As cerebral organoids (mini-brains) become more complex, exhibiting brain waves similar to preterm infants, science faces a profound question: At what point does biological complexity become sentience?

Harnessing evolution: Evolved synthetic disordered proteins could address disease, antibiotic resistance

Yifan Dai and his team designed a method based on directed evolution to create synthetic intrinsically disordered proteins that can facilitate diverse phase behaviors in living cells. Intrinsically disordered proteins have different phase behaviors that take place at increasing or decreasing temperatures, as shown in the image above. The intrinsically disordered proteins on the left are cold responsive, and those on the right are hot responsive. The tree image in the center depicts the directed evolution process with the reversible intrinsically disordered proteins near the top. Feeding into the process from the bottom are soluble intrinsically disordered proteins.
Illustration Credit: Dai lab

The increased prevalence of antibiotic resistance could make common infections deadly again, which presents a threat to worldwide public health. Researchers in the McKelvey School of Engineering at Washington University in St. Louis have developed the first directed evolution-based method capable of evolving synthetic condensates and soluble disordered proteins that could eventually reverse antibiotic resistance.

Yifan Dai, assistant professor of biomedical engineering, and his team designed a method that is directed evolution-based to create synthetic intrinsically disordered proteins that can facilitate diverse phase behaviors in living cells. This allows them to build a toolbox of synthetic intrinsically disordered proteins with distinct phase behaviors and features that are responsive to temperatures in living cells, which helps them to create synthetic biomolecular condensates. In addition to reversing antibiotic resistance, the cells can regulate protein activity among cells. 

Stem cell engineering breakthrough paves way for next-generation living drugs

UBC research associate Dr. Ross Jones in the lab where they are working to develop cell-based therapies from stem cells.
Photo Credit: Phillip Chin.

For the first time, researchers at the University of British Columbia have demonstrated how to reliably produce an important type of human immune cell—known as helper T cells—from stem cells in a controlled laboratory setting.  

The findings, published today in Cell Stem Cell, overcome a major hurdle that has limited the development, affordability and large-scale manufacturing of cell therapies. The discovery could pave the way for more accessible and effective off-the-shelf treatments for a wide range of conditions like cancer, infectious diseases, autoimmune disorders and more.   

“Engineered cell therapies are transforming modern medicine,” said co-senior author Dr. Peter Zandstra, professor and director of the UBC School of Biomedical Engineering. “This study addresses one of the biggest challenges in making these lifesaving treatments accessible to more people, showing for the first time a reliable and scalable way to grow multiple immune cell types.”  

Pills that communicate from the stomach could improve medication adherence

Two photos show the gelatin-coated capsules (left) and the capsule without the coating (right). The capsule can be broken down and absorbed by the body.
Photo Credit: Courtesy of the researchers
(CC BY-NC-ND 4.0)

In an advance that could help ensure people are taking their medication on schedule, MIT engineers have designed a pill that can report when it has been swallowed.

The new reporting system, which can be incorporated into existing pill capsules, contains a biodegradable radio frequency antenna. After it sends out the signal that the pill has been consumed, most components break down in the stomach while a tiny RF chip passes out of the body through the digestive tract.

This type of system could be useful for monitoring transplant patients who need to take immunosuppressive drugs, or people with infections such as HIV or TB, who need treatment for an extended period of time, the researchers say.