In this episode, we welcome Dr. Susanne Rafelski, a leading expert in cellular organization, to explore the complex interplay between gene expression and cellular phenotype. The challenge of understanding how a subset of expressed genes influences cellular phenotype is daunting due to the sheer number of involved molecules, their combinations, and the multitude of cellular behaviors they determine.

Dr. Rafelski's research reduces this complexity by focusing on cellular organization—a critical determinant and indicator of cell behavior. She introduces the WTC-11 hiPSC Single-Cell Image Dataset v1, a remarkable dataset containing over 200,000 live 3D cells across 25 key cellular structures. The scale and quality of this dataset have allowed for the creation of a comprehensive analysis framework to convert raw image data into dimensionally reduced, human-interpretable, quantitative measurements, promoting data exploration.

Dr. Rafelski talks us through how this framework harnesses the vast cell-to-cell variability seen within a normal population, integrates cell-by-cell structural data, and supports quantitative analyses of distinct aspects of organization within and across cell populations.

Her team found that the integrated intracellular organization of interphase cells remained robust amidst the wide range of variation in cell shape in the population. Furthermore, the average locations of some structures became polarized in cells at the colony edges while maintaining their 'wiring' with other structures.

Join us as we delve into the fascinating world of cellular organization and discover how changes in structure location during early mitotic reorganization are accompanied by changes in their wiring.

Key Words: Cellular Organization, Gene Expression, Cellular Phenotype, WTC-11 hiPSC Single-Cell Image Dataset v1, Data Analysis Framework, Cell Variability, Structural Data, Mitotic Reorganization.

Viana, M.P., Chen, J., Knijnenburg, T.A. et al. Integrated intracellular organization and its variations in human iPS cells. Nature 613, 345–354 (2023). https://doi.org/10.1038/s41586-022-05563-7

Slides: https://docs.google.com/presentation/d/1VO2SUjtnPV-6GvXboP1Uap1G2hKtSux0PEUoQwT7760/edit#slide=id.p1

In this episode, we speak with Dr. Vales-Colomer, a leading researcher in the field of microbiome science. Our conversation revolves around the human microbiome, its integral role in health, and the profound influence of interpersonal relationships on its genetic makeup.

Dr. Vales-Colomer delves into his latest research, based on an analysis of over 9,700 human metagenomes. This study reveals the intricate patterns of bacterial strain transmission between individuals, demonstrating the significant role of mother-to-infant transmission, intra-household sharing, and intra-population patterns. His findings suggest that approximately half of the bacterial strains in an infant's gut microbiome are transmitted from their mother, and this transmission remains detectable even in later life stages.

The conversation also touches upon the oral microbiome and the horizontal transmission that largely defines its makeup. Dr. Vales-Colomer highlights how cohabitation length influences strain sharing more significantly than age or genetics. Fascinatingly, his research also shows that bacterial strain-sharing patterns can better illustrate host population structures than species-level profiles.

Finally, Dr. Vales-Colomer discusses the identification of specific taxa that appear efficient in spreading across different transmission modes and their associated bacterial phenotypes linked to out-of-host survival capabilities.

Tune in to this episode for a fascinating journey into the world of the human microbiome and learn about the deep interplay between our microbes and social dynamics.

Key Words: Human Microbiome, Health, Interpersonal Relationships, Bacterial Strain Transmission, Mother-to-Infant Transmission, Intra-Household Sharing, Intra-Population Patterns, Cohabitation, Host Population Structures.

Valles-Colomer, M., Blanco-Míguez, A., Manghi, P. et al. The person-to-person transmission landscape of the gut and oral microbiomes. Nature (2023). https://doi.org/10.1038/s41586-022-05620-1

In this episode, we're joined by Dr. Ognjen Ilic, a leading scientist in the field of acoustic waves and metasurfaces, to discuss how waves exert force on obstacles in their path and how this can be manipulated. Conventionally, the radiation force exerted by waves is limited by the shape and size of the objects being manipulated. Dr. Ilic, however, has made a breakthrough discovery that challenges this fundamental rule.

Dr. Ilic explains how subwavelength-structured surfaces (metasurfaces) allow for the control of the radiation force exerted by acoustic waves, independent of the object's overall shape and size. The manipulation of this force is solely determined by the arrangement of the surface features on the metasurface.

We delve into Dr. Ilic's fascinating experiments demonstrating how this anomalous metasurface scattering can enable complex actuation phenomena such as self-guidance and tractor beaming. In self-guidance, a metasurface object is autonomously guided by an acoustic wave, while in tractor beaming, a metasurface object is pulled by the wave.

Join us as Dr. Ilic uncovers how the principles of metasurface acoustics can be applied to the domain of mechanical manipulation, ushering in new frontiers in contactless actuation and enabling diverse mechanisms that surpass the traditional limits of wave-matter interactions.

Key Words: Metasurface Acoustics, Acoustic Waves, Radiation Force, Anomalous Metasurface Scattering, Self-Guidance, Tractor Beaming, Contactless Actuation.

Stein, M., Keller, S., Luo, Y. et al. Shaping contactless radiation forces through anomalous acoustic scattering. Nat Commun 13, 6533 (2022). https://doi.org/10.1038/s41467-022-34207-7

In this episode, we welcome Dr. Kannan and his team, pioneers in neuroscience and the developers of Genetically Encoded Fluorescent Voltage Indicators (GEVIs). They share the intricate dynamics of signal processing in the brain, involving various excitatory and inhibitory neuron populations.

Dr. Kannan's team discusses their innovations, including the second-generation GEVIs Ace-mNeon2 and VARNAM2. These have shown significantly improved voltage sensitivities and, along with their respective reverse response-polarity variants, provide an unparalleled suite of tools for multi-population voltage recordings in awake, behaving animals.

The team also talks about their experiments involving these indicators, which allowed low-power recordings from a vast number of individual neurons in running mice. These investigations have unveiled fascinating insights into visual cortical cell type-specific responses to behavioral-state transitions. Their work has particularly highlighted the profound activation of cortical interneurons expressing somatostatin (SST) during a quiescence-to-arousal transition.

Dr. Kannan and his team have explored the functional dynamics of pairs of neuron types and the contributions of distinct cell classes to the local field potential in the hippocampus. They discovered differences in the responses of neuron subclasses to state changes and even extracted the simultaneous real-time voltage dynamics of three neuron types.

Join us in this episode as we delve into the insights gathered from the concerted dynamics of multiple cell classes in behaving animals. We also explore this technology's tremendous potential for furthering our understanding of brain function.

Key Words: Neuroscience, Genetically Encoded Fluorescent Voltage Indicators, Brain Function, Neuron Populations, Ace-mNeon2, VARNAM2, Visual Cortical Cell, Local Field Potential.

Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types https://doi.org/10.1126/science.abm8797

In this episode, we delve into the world of radiation biology with Dr. Siyao Wang. We explore the long-standing question of how paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring. This subject is of particular relevance considering that nearly 80% of transmitted mutations in humans arise from the paternal germline.

Dr. Wang shares insights from her research using Caenorhabditis elegans strains, which reveal that paternal, not maternal, exposure to ionizing radiation leads to transgenerational embryonic lethality. The offspring of irradiated males display numerous genome instability phenotypes, such as DNA fragmentation, chromosomal rearrangement, and aneuploidy. Intriguingly, the repair process for paternal DNA double strand breaks involves maternally provided error-prone polymerase theta-mediated end joining.

We further discuss the mechanisms that drive these outcomes, focusing on the roles of an orthologue of human histone H1.0, HIS-24, and the heterochromatin protein HPL-1. Dr. Wang elucidates how the depletion of these proteins can significantly reverse transgenerational embryonic lethality. She explains that the removal of HIS-24 or HPL-1 reduces histone 3 lysine 9 dimethylation and enables error-free homologous recombination repair in the germline of the F1 generation from ionizing radiation-treated P0 males, leading to improved viability of the F2 generation.

Tune into this episode to gain a deeper understanding of the heritable consequences of paternal radiation exposure, an area of research that could shed light on congenital disorders and cancer in humans.

Key Words: Radiation Biology, Paternal Radiation Exposure, Genetic Inheritance, Disease Risk, Transgenerational Embryonic Lethality, Genome Instability, DNA Fragmentation, Chromosomal Rearrangement, Aneuploidy, Homologous Recombination Repair, Histone H1.0, HIS-24, HPL-1.

Wang, S., Meyer, D.H. & Schumacher, B. Inheritance of paternal DNA damage by histone-mediated repair restriction. Nature (2022). https://doi.org/10.1038/s41586-022-05544-w

In this episode, we speak with Dr. Stoeger about one of the most profound phenomena in biology—aging. As a critical factor influencing morbidity and mortality, understanding the molecular mechanisms behind aging is of paramount importance.

Dr. Stoeger's research presents an intriguing perspective on this issue, revealing a strong relationship between transcript length and the transcriptional changes seen in aging in both mice and humans. It appears that as organisms age, there's a relative decrease in the abundance of long transcripts.

We delve into three compelling pieces of evidence that underscore the biological significance of this discovery. Firstly, this association of transcript length with aging is prevalent in vertebrates. Secondly, various anti-aging interventions have been shown to counter this length association, pointing to possible therapeutic avenues. Lastly, we learn about an intriguing enrichment pattern—genes with the longest transcripts are linked to lifespan extension, while those with the shortest transcripts are often associated with a shortened lifespan.

Join us as we unravel the secrets of aging and explore the complex organization of transcriptomes. It's an intriguing journey into the world of aging biology that you won't want to miss!

Key Words: Aging, Transcriptome, Transcript Length, Lifespan, Anti-Aging Interventions, Genes, Mice, Humans, Long Transcripts, Short Transcripts.

Stoeger, T., et al. Aging is associated with a systemic length-associated transcriptome imbalance. Nat Aging 2, 1191–1206 (2022). https://doi.org/10.1038/s43587-022-00317-6

In this episode, we sit down with Dr. Taverna to delve into the mysterious world of magnetars—neutron stars with ultra-strong magnetic fields. While magnetars are primarily observed at x-ray wavelengths, the precise mechanisms and geometry of the emitting regions have remained a puzzle.

Dr. Taverna discusses their ground-breaking research that has taken a novel approach to studying these celestial bodies: measuring the x-ray polarization of the magnetar 4U 0142+61. These measurements revealed a fascinating and complex picture. The polarization degree and angle both change as a function of x-ray energy, pointing towards two distinct emission regions.

The conversation dives into the preferred model where most of the x-rays are emitted by an equatorial band on the neutron star's surface. Some photons then undergo scattering to higher energies due to collisions with electrons in the surrounding magnetic field. This reprocessing of thermal radiation provides new insights into the properties of the magnetar's magnetic fields and surface.

Join us as we uncover the secrets of magnetar emissions, guided by the intriguing insights drawn from x-ray polarization. It's an astronomical journey you don't want to miss!

Key Words: Magnetars, Neutron Stars, X-ray Polarization, Emission Regions, Magnetic Fields, Scattering, 4U 0142+61, Equatorial Band, Charged Particles, Magnetosphere.

https://doi.org/10.1126/science.add0080

In this enlightening episode, we engage in an in-depth conversation with Dr. Xu about his recent groundbreaking work on the quantization of linearly polarized photons from the Lorentz-boosted electromagnetic field of a nucleus traveling at ultrarelativistic speed.

Dr. Xu's experiment investigates a fascinating scenario where two relativistic heavy nuclei pass each other at a distance of a few nuclear radii. The photon from one nucleus can interact with the gluons of the other through a virtual quark-antiquark pair, forming a short-lived vector meson, such as ρ0. This process, termed diffractive photoproduction, is used to observe a unique spin interference pattern in the angular distribution of ρ0 → π+π− decays.

In an intriguing display of quantum mechanics, the observed interference results from the overlap of two wave functions at a distance that's an order of magnitude larger than the travel distance of the ρ0 within its lifetime. From these diffractive interactions, Dr. Xu and his team extracted the strong-interaction nuclear radii of 197Au and 238U, which were found to be larger than the nuclear charge radii.

Join us as we delve into the quantum realm to understand how this observable can shed light on nuclear geometry and the quantum interference of nonidentical particles. It's an episode filled with profound insights about the fundamental nature of matter and forces!

Key Words: Linearly Polarized Photon, Lorentz-Boosted Electromagnetic Field, Nuclear Radii, Quantum Interference, Diffractive Photoproduction, Spin Interference, Nuclear Geometry.

Tomography of ultrarelativistic nuclei with polarized photon-gluon collisions https://doi.org/10.1126/sciadv.abq3903

In this enlightening episode, we chat with Dr. Elinav about his fascinating research on the association of certain gut microbes with inflammatory bowel diseases (IBD) and the potential use of phage therapy to combat these conditions.

Dr. Elinav's work focuses on a clade of Klebsiella pneumoniae (Kp) strains, found to be associated with the severity and exacerbation of IBD in four distinct geographical cohorts. These strains, unique in their antibiotics resistance and mobilome signature, were observed to enhance intestinal inflammation when transferred into colitis-prone, germ-free, and colonized mice.

Exploring the potential of phage therapy, Dr. Elinav and his team have designed a lytic five-phage combination that targets both sensitive and resistant members of the IBD-associated Kp clade, and effectively suppresses Kp in colitis-prone mice, leading to decreased inflammation and disease severity.

Our conversation also covers the proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers, demonstrating the resilience, safety, and viability of these phages in the lower gut.

Join us as we delve into the promise of phage therapy for managing gut microbes contributing to non-communicable diseases, a new frontier in IBD treatment.

Key Words: Inflammatory Bowel Diseases, Klebsiella pneumoniae, Phage Therapy, Gut Microbiota, Pathobionts, Antibiotic Resistance, Non-Communicable Diseases.

Dr. Elinav et al.: Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation https://doi.org/10.1016/j.cell.2022.07.003

In this intriguing episode, we have a conversation with Dr. Ari Benjamin, focusing on the parallels between human sensory systems and artificial neural networks in terms of their sensitivity to common features in the environment.

Human sensory systems are notably more sensitive to common environmental features, and Dr. Benjamin's research reveals that artificial neural networks trained in object recognition demonstrate similar sensitivity patterns aligned with the statistics of image features.

Dr. Benjamin explains a mathematical interpretation of these findings, showing that learning with gradient descent in neural networks preferentially forms representations that are more sensitive to common features, a characteristic of efficient coding. This effect appears in systems with otherwise unconstrained coding resources and occurs when learning towards both supervised and unsupervised objectives.

Through our discussion, we delve into the notion that efficient codes can naturally emerge from gradient-like learning, highlighting the connections between human perception and AI learning mechanisms.

Key Words: Artificial Intelligence, Sensory Perception, Gradient Descent, Neural Networks, Efficient Coding, Object Recognition, Supervised Learning, Unsupervised Learning.

Benjamin, A.S., Zhang, LQ., Qiu, C. et al. Efficient neural codes naturally emerge through gradient descent learning. Nat Commun 13, 7972 (2022). https://doi.org/10.1038/s41467-022-35659-7