Dr. Robin J. Malloy’s Post

✨ Imagine if we could have a remote control for our cells — just like we do for our TVs 📺 — allowing us to control cell functions for diagnostic and therapeutic purposes! ✨   At the PSI Center for Life Sciences, researchers are developing a new form of #optogenetics as part of the Switchable RhodOpsins in Life Sciences (SOL) project, which has received a coveted #ERC grant of nearly eight million euros from the European Research Council (ERC). They are utilizing receptors similar to the #rhodopsins found in our eyes—these receptors activate with light 💡 and initiate specific cellular signaling processes.   PSI researchers have made significant progress towards SOL's goals, as reported in two new studies:   ✔️ In one study published in the journal PNAS, they elucidated the structure of special photoreceptors thanks to the unique capabilities of PSI’s high-resolution large research facilities, which enable detailed structural analysis. Full paper: https://lnkd.in/dssvNqNJ ✔️ In a second study featured in Nature Communications, they genetically modified a light receptor, ensuring that switching on and off now occurs with different colors of light. 🌈 Full paper: https://lnkd.in/d2xdV6Sx   This is amazing work 👏 , although the most substantial part of the protein engineering is still ahead. Ultimately, the goal is to assemble a comprehensive toolkit of light-activated receptor for various applications in the organism. 🚀💪 Ream more here: https://lnkd.in/d2hyjSU4 #HealthInnovations #Medicine #Biology #Diagnostics #Neuroscience   CC: Oliver Tejero, Ching-Ju Tsai, Gebhard F. X. Schertler and Matthew Rodrigues

🚨 Surprising breakthrough in Neuroscience: Overcoming the Blood-Brain Barrier! 🧠 In the field of neuroscience, one of the biggest challenges in treating neurological diseases is the blood-brain barrier (BBB)—a highly selective membrane that regulates the transfer of solutes and chemicals, such as various nutrients, ions, organic anions, small drugs and macromolecules such as glucose and amino acids, between the blood circulation and the brain. While the BBB protects the brain from harmful substances, it also prevents larger therapeutic molecules and drugs from reaching their targets, limiting their effectiveness. But there’s exciting news on the horizon! 🌟 An international team of scientists from Tel Aviv and Glasgow Universities has has made a groundbreaking innovation: they’ve genetically engineered the parasite Toxoplasma gondii to deliver therapeutic proteins across the BBB! Known as the ‘cat parasite,’ Toxoplasma gondii has the unique ability to penetrate the human brain and remain dormant, making it an ideal candidate for this novel approach. In the study, researchers modified the parasite’s DNA to produce and secrete the desired therapeutic proteins directly into the brain. They successfully delivered the MeCP2 protein —essential for treating Rett syndrome—in animal models.  This research, published in Nature Microbiology, opens up new possibilities for addressing protein deficiencies in neurological disorders. While this innovative approach holds immense potential, it also raises important safety concerns if it moves to clinical trials. This is a significant step forward in the fight against neurological diseases, and it could revolutionize how we approach drug delivery to the brain! What do you think about this innovation? Source: Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons #Neuroscience #BloodBrainBarrier #ToxoplasmaGondii #parasite #NeurologicalDisorders #MedicalInnovation #DrugDelivery #RettSyndrome #ResearchBreakthrough #HealthcareInnovation #genetic #biomedical #innovation #nature #naturemicrobiology #sciencecommunication #interesting #weird

☑️ *READ ABSTRACT BELOW:* Three-dimensional (3D) organoid cultures are flexible systems to interrogate cellular growth, morphology, multicellular spatial architecture, and cellular interactions in response to treatment. However, computational methods for analysis of 3D organoids with sufficiently high-throughput and cellular resolution are needed. Here we report Cellos, an accurate, high-throughput pipeline for 3D organoid segmentation using classical algorithms and nuclear segmentation using a trained Stardist-3D convolutional neural network. To evaluate Cellos, we analyze ~100,000 organoids with ~2.35 million cells from multiple treatment experiments. Cellos segments dye-stained or fluorescently-labeled nuclei and accurately distinguishes distinct labeled cell populations within organoids. Cellos can recapitulate traditional luminescence-based drug response of cells with complex drug sensitivities, while also quantifying changes in organoid and nuclear morphologies caused by treatment as well as cell-cell spatial relationships that reflect ecological affinity. Cellos provides powerful tools to perform high-throughput analysis for pharmacological testing and biological investigation of organoids based on 3D imaging. Mukashyaka P, Kumar P, Mellert DJ, Nicholas S, Noorbakhsh J, Brugiolo M, Courtois ET, Anczukow O, Liu ET, Chuang JH. High-throughput deconvolution of 3D organoid dynamics at cellular resolution for cancer pharmacology with Cellos. Nat Commun. 2023 Dec 18;14(1):8406. doi: 10.1038/s41467-023-44162-6. PMID: 38114489; PMCID: PMC10730814. #Gesundheit #Bildung #Fuehrung #Coaching #Mindset #Motivation #Gehirn #Neuroscience #Psychologie #Persoenlichkeitsentwicklung #Kindheit #KeyNoteSpeaker #Humangenetik #Biochemie #Neuroleadership #Ernaehrung #Transformation #Stress #Demografie #Gender #Age #interkulturelleKompetenz #Epigenetik #Veraenderung #EmotionaleIntelligenz #Change #Gesellschaft #Organisationsentwicklung #Philosophie #Beratung # Quantum

📃Scientific paper: Thyroid hormone rewires cortical circuits to coordinate body-wide metabolism and exploratory drive Abstract: Animals adapt to varying environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here we find that thyroid hormone— a prominent regulator of metabolism in many peripheral organs— activates cell-type specific transcriptional programs in anterior regions of cortex of adult mice via direct activation of thyroid hormone receptors. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulators across both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread remodeling of cortical circuits. Indeed, whole-cell electrophysiology recordings revealed that thyroid hormone induces local transcriptional programs that rewire cortical neural circuits via pre-synaptic mechanisms, resulting in increased excitatory drive with a concomitant sensitization of recruited inhibition. We find that thyroid hormone bidirectionally regulates innate exploratory behaviors and that the transcriptionally mediated circuit changes in anterior cortex causally promote exploratory decision-making. Thus, thyroid hormone acts directly on adult cerebral cortex to coordinate exploratory behaviors with whole-body metabolic state. Continued on ES/IODE ➡️ https://etcse.fr/kDp ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

#ScienceFridays 🔬 Research paper of the week ➡ ‘Leveraging spatial omics for the development of precision sarcoma treatments’ 🔎 Abstract: Researchers in this study explored how recent advances in spatial #omics technologies have enabled a more comprehensive study of the sarcoma tumor microenvironment (TME) and can potentially facilitate the application of #PrecisionMedicine to treat pediatric #Sarcoma, a variant of rare and heterogeneous cancers that affects mostly children and adolescents. ✍️ Authors: Cui Tu, Arutha Kulasinghe, Andrew Barbour and Fernando Guimaraes. 🏫 Affiliations: Frazer Institute and the Princess Alexandra Hospital at The University of Queensland. 📄 Published on: Trends in Pharmacological Sciences (Cell Press) Find the link to the article on our #DrugRepurposing Research Collection, curated via ScienceOpen 🔗 https://lnkd.in/g42rZ6Va #FutureOfMedicine #OpenScience #CancerResearch #CancerTreatments

🔬 Academic Seminar Highlight: Excited to have attended an insightful seminar on "Cardiac Structure and Functional Plasticity: Unveiling New Molecules and Mechanisms" at Shanghai Jiao Tong University's School of Biomedical Engineering. 🗣 Speaker: Dr. Fujian Lu, Researcher 📅 Date & Time: March 14th, 14:00-15:40 📍 Location: Engineering Building 100, Xuhui Campus, Shanghai Jiao Tong University 📝 Abstract: Dr. Lu's presentation delved into the intricate dynamics of excitation-contraction coupling (ECC) in the heart, focusing on the pivotal role of dyads and their protein constituents. Understanding the formation, regulation, and implications of dyad structures is crucial for unraveling novel theories in ECC and calcium signaling, as well as for developing innovative treatments for cardiac diseases. 👨🏫 About the Speaker: Dr. Fujian Lu is a dual-appointed young researcher at Fudan University's Institute of Biomedical Sciences and Zhongshan Hospital. His research interests span spatial-temporal calcium signaling regulation systems, targeted drug development for calcium channelopathies, and gene therapy for cardiac diseases. 📚 Research Highlights: Dr. Lu's research group has made significant contributions to calcium probe development, multi-dimensional calcium imaging, cancer metastasis regulation, ECC regulation, and gene therapy for cardiac diseases, with publications in esteemed journals including Circulation, Nature Communications, and Circulation Research. Kudos to Dr. Lu and his team for their groundbreaking research in advancing our understanding of cardiac physiology and pathology. Looking forward to more enlightening discussions in the future! #biomaterials #regenerativemedicine #genetherapy #biomedicalengineering #biotechnology #MedicalRobotics #AcademicSeminar #HealthTech #shanghai #Innovation #china #c9league

☑️ *READ ABSTRACT BELOW:* Keywords: Cell-free DNA biology; Extrachromosomal circular DNA; Fragmentomics; In vitro models; Organoids Part 1: Background: Fragmentomics, the investigation of fragmentation patterns of cell-free DNA (cfDNA), has emerged as a promising strategy for the early detection of multiple cancers in the field of liquid biopsy. However, the clinical application of this approach has been hindered by a limited understanding of cfDNA biology. Furthermore, the prevalence of hematopoietic cell-derived cfDNA in plasma complicates the in vivo investigation of tissue-specific cfDNA other than that of hematopoietic origin. While conventional two-dimensional cell lines have contributed to research on cfDNA biology, their limited representation of in vivo tissue contexts underscores the need for more robust models. In this study, we propose three-dimensional organoids as a novel in vitro model for studying cfDNA biology, focusing on multifaceted fragmentomic analyses.(...) Kim J, Hum Genomics. 2023 Oct 28;17(1):96. doi: 10.1186/s40246-023-00533-0. PMID: 37898819; PMCID: PMC10613368. #Gesundheit #Bildung #Fuehrung #Coaching #Mindset #Motivation #Gehirn #Neuroscience #Psychologie #Persoenlichkeitsentwicklung #Kindheit #KeyNoteSpeaker #Humangenetik #Biochemie #Neuroleadership #Ernaehrung #Transformation #Stress #Demografie #Gender #Age #interkulturelleKompetenz #Epigenetik #Veraenderung #EmotionaleIntelligenz #Change #Gesellschaft #Organisationsentwicklung #Philosophie #Beratung # Quantum

📃Scientific paper: Thyroid hormone rewires cortical circuits to coordinate body-wide metabolism and exploratory drive Abstract: Animals adapt to varying environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here we find that thyroid hormone— a prominent regulator of metabolism in many peripheral organs— activates cell-type specific transcriptional programs in anterior regions of cortex of adult mice via direct activation of thyroid hormone receptors. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulators across both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread remodeling of cortical circuits. Indeed, whole-cell electrophysiology recordings revealed that thyroid hormone induces local transcriptional programs that rewire cortical neural circuits via pre-synaptic mechanisms, resulting in increased excitatory drive with a concomitant sensitization of recruited inhibition. We find that thyroid hormone bidirectionally regulates innate exploratory behaviors and that the transcriptionally mediated circuit changes in anterior cortex causally promote exploratory decision-making. Thus, thyroid hormone acts directly on adult cerebral cortex to coordinate exploratory behaviors with whole-body metabolic state. Continued on ES/IODE ➡️ https://etcse.fr/kDp ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

☑️ *READ ASTRACT BELOW:* Part 2: Bulk RNA sequencing indicated that separation by cell type (A2B5-positive vs mature oligodendrocytes) is more significant than by region but segregation for each cell type by region is apparent. Molecular features of grey matter versus white matter derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter derived cells with relevance for myelination included those related to responses to external environment, cell-cell communication, cell migration, and cell adhesion. Immune and cell death related genes were up-regulated in grey matter derived cells. We observed a significant number of up-regulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, likely reflecting the plasticity of these cells ex vivo. The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage. Cui QL, Brain. 2024 Oct 8:awae311. doi: 10.1093/brain/awae311. Epub ahead of print. PMID: 39378316. #Gesundheit #Bildung #Fuehrung #Coaching #Mindset #Motivation #Gehirn #Neuroscience #Psychologie #Persoenlichkeitsentwicklung #Kindheit #KeyNoteSpeaker #Humangenetik #Biochemie #Neuroleadership #Ernaehrung #Transformation #Stress #Demografie #Gender #Age #interkulturelleKompetenz #Epigenetik #Veraenderung #EmotionaleIntelligenz #Change #Gesellschaft #Organisationsentwicklung #Philosophie #Beratung # Quantum

Exciting Research Alert from SMLS, Sunway University We are proud to share the research work by our Master of Life Science candidate, Shin Jie Yong, and supervisory team from SMLS and National University of Malaysia (UKM), Prof. Abhimanyu Veerakumarasivam, Assoc. Prof. Seong Lin Teoh, Assoc. Prof. Lim Wei Ling, and Assoc. Prof. Jactty Chew. 🧬 Lactoferrin Protects Against Rotenone-Induced Toxicity in Dopaminergic SH-SY5Y Cells through the Modulation of Apoptotic-Associated Pathways This study offers new hope in the fight against Parkinson's disease (PD), a neurodegenerative disorder with limited therapeutic options. The research showcases lactoferrin’s potential in protecting neurons from rotenone-induced toxicity—a naturally occurring environmental toxin linked to increased PD risk in humans. 🔬 The team discovered that lactoferrin pre-treatment significantly reduced cell death, mitochondrial impairment, and pro-apoptotic activities in dopaminergic neurons exposed to rotenone. Their findings highlight the modulation of critical apoptotic pathways, suggesting lactoferrin as a promising candidate for PD therapy. This is an important step forward for neuroprotective treatments and highlights the innovation happening here at Sunway University! #ParkinsonsResearch #Neuroprotection #Lactoferrin #MedicalResearch #SunwayUniversity #SMLS #Biotechnology #Neuroscience #Innovation