Science Society

Join us in this episode as we host Dr. McCracken, a leading figure in kidney regenerative medicine. Dr. McCracken shares his team's remarkable findings in the directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia, which is a pivotal step in the field of kidney regenerative medicine.

We begin our discussion by understanding how hPSCs are induced into pronephric progenitor cells with a 90% efficiency rate. These cells are then aggregated into spheres that closely resemble the molecular signature of the nephric duct. Within a three-dimensional matrix, these spheres develop into ureteric bud (UB) organoids that exhibit similar branching morphogenesis to the fetal UB and correct distal tip localization of RET expression.

Dr. McCracken explains how the cells derived from these organoids successfully incorporate into the UB tips in chimeric fetal kidney explant culture. In the later stages, UB organoids differentiate into CD organoids, which contain more than 95% CD cell types, as estimated by single-cell RNA sequencing.

Impressively, the CD epithelia demonstrate renal electrophysiologic functions, including ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells.

Through our conversation with Dr. McCracken, listeners will gain a deeper understanding of this groundbreaking research and its implications for kidney regenerative medicine.

Keywords: Kidney Regenerative Medicine, Human Pluripotent Stem Cells, hPSCs, Ureteric Bud, UB Organoids, Collecting Duct, CD Epithelia, Nephric Duct, ENaC, FOXI1.

McCracken, et al. Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types. 2022 https://doi.org/10.1038/s41587-022-01429-5

Join us for an enlightening episode featuring Dr. Miller, who shares his research focusing on the impact of mitochondrial DNA variants, particularly mitochondrial SNP rs2853499, on Alzheimer's Disease (AD), neuroimaging, and transcriptomics.

Dr. Miller's team successfully mapped this SNP to a new mitochondrial small open reading frame called SHMOOSE, which has the potential to encode a microprotein. For the first time ever, they have detected two unique SHMOOSE-derived peptide fragments in mitochondria using mass spectrometry, marking an exciting breakthrough in the detection of mitochondrial-encoded microproteins.

We delve into how levels of SHMOOSE in human cerebrospinal fluid (CSF) correlate with age, CSF tau, and brain white matter volume, providing crucial insight into the potential role of this microprotein in the onset and progression of AD.

Dr. Miller also discusses the results of functional experiments his team conducted. These revealed that SHMOOSE acted on the brain following intracerebroventricular administration, influenced mitochondrial gene expression in multiple models, localized to mitochondria, bound the inner mitochondrial membrane protein mitofilin, and enhanced mitochondrial oxygen consumption.

In this episode, listeners will gain a comprehensive understanding of Dr. Miller's groundbreaking work and its profound implications for the fields of neurobiology, Alzheimer’s disease, and microproteins.

Keywords: Alzheimer's Disease, Mitochondria, Microproteins, Mitochondrial DNA variants, SHMOOSE, Neuroimaging, Transcriptomics, Mitofilin, Neurobiology.

Miller, B., et al. Mitochondrial DNA variation in Alzheimer’s disease reveals a unique microprotein called SHMOOSE. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01769-3

Title: Revolutionizing Neuroscience: Wireless, Battery-free Optofluidics with Dr. Wu

Description: On this episode, we're delighted to host Dr. Wu, who is at the forefront of developing innovative solutions for controlling neuronal activity in neuroscience research. His groundbreaking work centers on in vivo optogenetics and photopharmacology, techniques with vast potential but limited applicability due to the lack of suitable tools.

Dr. Wu introduces us to a wireless, battery-free, programmable multilateral optofluidic platform designed for user-selected applications in optogenetics, pharmacology, and photopharmacology. This system boasts mechanically compliant microfluidic and electronic interconnects and offers dynamic control over drug delivery rates. Notably, it can be programmed in real-time to simultaneously control up to 256 separate devices within a single cage environment.

Our conversation then dives into the potential of this technology in manipulating animal behavior. Dr. Wu shares results from his team's behavioral experiments, where they successfully controlled motor behaviors in grouped mice via in vivo optogenetics coupled with localized gene delivery and the controlled photolysis of caged glutamate.

Join us as we delve into the future of neuroscience with Dr. Wu, exploring the many ways this optofluidic system can expand the scope of wireless techniques in the study of neural processing in animal models.

Keywords: Neuroscience, Optogenetics, Phytopharmacology, Wireless Techniques, Battery-free, Optofluidics, Neurobiology, In Vivo Studies, Gene Delivery.

Wireless multi-lateral optofluidic microsystems for real-time programmable optogenetics and photopharmacology Nat Commun 13, 5571 (2022). https://doi.org/10.1038/s41467-022-32947-0

In this episode, we dive deep into the mysteries of ancient Chinese bronze casting with our esteemed guests, Dr. Liu and Professor Pollard. The duo brings to light an intriguing aspect of archaeological research—understanding ancient alloying practices, key to the mass production of Chinese bronzes.

Our discussion centers around the Rites of Zhou, an Eastern Zhou text which has perplexed researchers for more than a century. It contains six formulae, or recipes, for casting different forms of bronze using two components: Jin and Xi. The exact interpretation of these components has remained elusive, leaving a gap in our comprehension of early metallurgical practices.

Dr. Liu and Professor Pollard present a novel interpretation derived from their analyses of pre-Qin coinage. They propose that Jin and Xi were not pure metals as previously thought but pre-prepared copper-rich alloys. This suggests an additional, unaccounted step in the manufacturing process of copper-alloy objects, altering our understanding of this ancient technology.

Join us as we unravel the intricacies of Chinese metallurgy with Dr. Liu and Professor Pollard, a journey of discovery that promises to fascinate linguists and archaeologists alike.

Keywords: Ancient Chinese Bronze, Alloying Practices, Archaeology, Metallurgy, Rites of Zhou, Jin, Xi, Copper-rich Alloys, Pre-Qin Coinage.

Cambridge University: Pollard, A., & Liu, R. (2022). The six recipes of Zhou: A new perspective on Jin (金) and Xi (锡). Antiquity, 1-14. doi:10.15184/aqy.2022.81

In this episode, we're exploring the fascinating intersection of nanotechnology and biology with Dr. Boghossian, who has been delving into the remarkable properties and potential of single-walled carbon nanotubes (SWCNTs) for cell nanobiotechnology.

Our discussion revolves around Dr. Boghossian's groundbreaking work examining the uptake of SWCNTs in Gram-negative cyanobacteria. Her research uncovers a passive length-dependent and selective internalization of SWCNTs decorated with positively charged biomolecules, a previously unexplored aspect of SWCNT functionalization for transport across prokaryotic cell walls.

Notably, her team showed that lysozyme-coated SWCNTs spontaneously penetrate the cell walls of both unicellular and multicellular strains. Using a custom-built spinning-disc confocal microscope, they were able to image the distinct near-infrared SWCNT fluorescence within the autofluorescent cells, revealing a highly inhomogeneous distribution of SWCNTs.

Dr. Boghossian's work also dives into the biotechnological implications of this research. For example, she found that the nanobionic cells not only retained photosynthetic activity but also showed an improved photo-exoelectrogenicity when incorporated into bioelectrochemical devices.

Join us in this episode as we journey through this innovative domain of cell nanobiotechnology with Dr. Boghossian.

Keywords: Single-Walled Carbon Nanotubes, SWCNTs, Cell Nanobiotechnology, Cyanobacteria, Functionalization, Lysozyme-Coated SWCNTs, Nanobionic Cells, Photosynthetic Activity, Bioelectrochemical Devices.

Antonucci, et al. Carbon nanotube uptake in cyanobacteria for near-infrared imaging and enhanced bioelectricity generation in living photovoltaics. (2022). https://doi.org/10.1038/s41565-022-01198-x

Social touch is an integral part of communication among many species, yet understanding the underlying pathways and mechanisms remains an intricate challenge. In this episode, we are joined by Dr. Dobolyi, whose research has brought new light to this fascinating area.

Dr. Dobolyi's study revolves around the discovery of a novel neuronal pathway from the posterior intralaminar thalamic nucleus (PIL) to the medial preoptic area (MPOA) that plays a key role in controlling social grooming. The groundbreaking findings reveal that neurons in both the PIL and MPOA activate naturally through physical contact between female rats or chemogenetic stimulation of PIL neurons. Interestingly, these neurons were found to express the neuropeptide parathyroid hormone 2 (PTH2), and it was observed that central infusion of its receptor antagonist diminished social grooming.

Intriguingly, the study also shows a similarity in the anatomical organization of the PIL and the distribution of the PTH2 receptor in the MPOA between rat and human brains, suggesting this pathway's potential relevance in human social behavior.

Join us as we delve deep into the world of neurobiology, exploring the intricacies of social interaction and grooming behavior with Dr. Dobolyi.

Keywords: Social Grooming, Posterior Intralaminar Thalamic Nucleus, Medial Preoptic Area, Neuronal Pathway, Parathyroid Hormone 2, Neurobiology, Social Behavior.

A thalamo-preoptic pathway promotes social grooming in rodents https://doi.org/10.1016/j.cub.2022.08.062 Social interaction increases activity in the posterior thalamus (PIL)

Monitoring the release of neurotransmitters at spatial and temporal scales relevant to neuron function has always been a scientific challenge. This episode welcomes Dr. Beyene, who has developed an innovative solution to improve our understanding of chemical neurotransmission.

Dr. Beyene's groundbreaking research revolves around a chemi-sensitive, two-dimensional composite nanofilm that allows for the visualization of neurochemical dopamine release with unprecedented synaptic resolution and quantal sensitivity. This cutting-edge technology enables the observation of neurotransmitter release from hundreds of sites simultaneously, making it possible to monitor the spatiotemporal dynamics of dopamine release in dendritic processes—a phenomenon that has, until now, been poorly understood.

One of the most significant discoveries was that dopamine release is 'broadcast' from a subset of dendritic processes, referred to as 'hotspots.' These hotspots were found to co-localize with Bassoon, a protein known for organizing active zones in axon terminals. This suggests that Bassoon may also contribute to organizing active zones in dendrites.

Join us as we delve deep into the world of neurotransmission, exploring the intricacies of dopamine release, and discussing the possible implications of Dr. Beyene's findings for our understanding of neuronal communication.

Keywords: Neurotransmission, Dopamine, Composite Nanofilm, Synaptic Resolution, Dendritic Processes, Bassoon, Neuronal Communication.

Visualizing synaptic dopamine efflux with a 2D composite nanofilm https://doi.org/10.7554/eLife.78773

In this riveting episode, we delve into the intricacies of glioblastoma, a devastating and incurable type of brain tumor, with Dr. Varun Venkataramani. A key focus of the discussion centers around his groundbreaking research on tumor cell networks and the surprising influence of neuronal mechanisms on glioblastoma cell invasion.

Dr. Venkataramani's team discovered that certain glioblastoma cells lack connections with other tumor cells and astrocytes but intriguingly receive synaptic input from neurons. These cells, identified to correspond to neuronal and neural-progenitor-like tumor cell states via single-cell transcriptomics, appear to be responsible for whole-brain colonization. This discovery is consistent with both mouse models and observations in human patients.

The team found that tumor cell invasion seems to mimic neuronal migration mechanisms, adopting a Lévy-like movement pattern as they explore their environment. Furthermore, neuronal activity was seen to trigger complex calcium signals in glioblastoma cells, leading to the formation of tumor microtubes (TMs) and an increase in invasion speed.

Dr. Venkataramani's research provides a profound insight into the intricate relationship between glioblastoma dissemination and cellular heterogeneity, highlighting the instrumental role neuronal mechanisms play in these processes.

Join us in this fascinating conversation as we delve deeper into the complexities of glioblastoma invasion and the potential implications of these findings for future treatment strategies.

Keywords: Glioblastoma, Neuronal Mechanisms, Tumor Cell Networks, Invasion, Tumor Microtubes, Single-cell Transcriptomics, Brain Tumors.

Venkataramani V et al. Glioblastoma hijacks neuronal mechanisms for brain invasion. Cell. 2022 Aug 4;185(16):2899-2917.e31. doi: 10.1016/j.cell.2022.06.054. Epub 2022 Jul 31. PMID: 35914528.

In this episode, we explore how groundbreaking scientific advancements are providing solutions to prevent injury to the cardiac conduction system (CCS) during heart surgeries, a critical yet elusive network of cells embedded within the heart. Our guest, Dr. Goodyer, is leading the charge in this domain.

Dr. Goodyer's team has engineered targeted antibody-dye conjugates that specifically bind to the CCS, enabling its visualization in mice in vivo with high sensitivity, specificity, and resolution. This development provides the potential to avoid accidental damage to the CCS during cardiac procedures.

Expanding on this innovation for human use, Dr. Goodyer's team developed a fully human monoclonal Fab that targets the CCS with high specificity. Interestingly, this Fab can also be used to modulate CCS biology when linked to a different cargo, paving the way for potential targeted cardiac therapies.

Furthermore, through differential gene expression analysis of the entire murine CCS at single-cell resolution, the team identified and validated a set of additional cell surface markers. These can molecularly target distinct subcomponents of the CCS, aiding in the management of specific, life-threatening arrhythmias.

Join us as we delve into the intricacies of these breakthroughs with Dr. Goodyer and discuss their potential to revolutionize cardiac imaging, cardiothoracic surgery, and arrhythmia management.

Keywords: Cardiac Conduction System, Cardiac Surgery, Antibody-Dye Conjugates, Monoclonal Fab, CCS Imaging, Targeted Cardiac Therapies, Arrhythmia.

In vivo visualization and molecular targeting of the cardiac conduction system. J Clin Invest. 2022 Aug 11:e156955. doi: 10.1172/JCI156955. Epub ahead of print. PMID: 35951416.

In this episode, we are joined by Dr. Howard Salis, who has been pioneering research on the complex mechanisms governing transcription rates in bacteria. The focus of our discussion is his team's recent breakthrough in predicting site-specific transcription initiation rates for any σ70 promoter sequence in bacteria.

A critical challenge in the field has been understanding how non-canonical sequence motifs collectively control transcription rates. Dr. Salis' team ingeniously used a combination of massively parallel assays, biophysics, and machine learning to develop a 346-parameter model. This model, validated across 22,132 bacterial promoters with diverse sequences, holds the potential to unravel the intricate processes of gene regulation in natural genetic systems.

The model's application extends to predicting genetic context effects, designing σ70 promoters with specific transcription rates, and identifying undesired promoters within engineered genetic systems. This breakthrough provides a new level of precision in transcriptional control, which is crucial for the engineering of synthetic genetic systems.

Join us as Dr. Salis illuminates the world of bacterial transcription and the role it plays in both nature and the realm of synthetic biology.

Keywords: Bacterial Transcription, Gene Regulation, Synthetic Biology, Machine Learning, Biophysics, σ70 Promoter, Genetic Systems, Dr. Howard Salis.

Automated model-predictive design of synthetic promoters to control transcriptional profiles in bacteria. Nat Commun 13, 5159 (2022). https://doi.org/10.1038/s41467-022-32829-5