UC San Diego Center for Precision Computational Systems Network (PreCSN)

The UC San Diego UC San Diego Agilent Center of Excellence in Cellular Intelligence's weekly series--#DidYouKnow--features examples of how you can push the limits of #Measurements-#Across-#Scales. This is our 19th post of this series and it is about GASOTRANSMITTORS and how we therapeutically modulate the same. #DidYouKnow that "Gasotransmittors" are gaseous molecules our body naturally produces to regulate vital biological processes? Just like other second messengers (such as cyclic AMP or calcium), these molecules must stay within a goldilocks range—too little or too much can be harmful. Some key gasotransmittors include Nitric Oxide (NO), Carbon Monoxide (CO), and Hydrogen Sulfide (H?S)—each playing critical roles in cellular signaling and homeostasis. This week, the UC San Diego Institute for Network Medicine (iNetMed) is tackling an actionable insight recently discovered by the UC San Diego Center for Precision Computational Systems Network (PreCSN) using AI/ML approaches. Their research identified a common underlying defect in #gut mucosal #bioenergetics—captured by a 34-gene #signature—as a driver of #therapeutic #resistance in #Inflammatory #Bowel #Diseases (#IBD) across all #drug classes. The team hypothesized that restoring this bioenergetic balance, which appeared to be induced by excessive production of a key gastrotransmitter by both #gutmicrobes and colon epithelium could be a novel therapeutic strategy. To test this, they collaborated with: ?? UC San Diego HUMANOID: Center of Excellence in Human Organoid Research to model bioenergetic failure in IBD #organoids (#PDOs) ?? UC San Diego Agilent Center of Excellence in Cellular Intelligence to translate the 34-gene defect into a #functional #readout ?? #Results? The team successfully recreated the complexity of gasotransmitter-induced oxygen consumption rate (OCR) suppression in #CrohnsDisease PDOs—and demonstrated a near-complete reversal using a #drug that selectively chelates excess gasotransmitters. Exciting steps forward in #precisionmedicine for IBD! ???? #IBD #PrecisionMedicine #Gasotransmitters #Organoids #AIinBiology #NetworkMedicine #Bioenergetics #Gastroenterology This work is possible because of a #Computational #Immunology Program that is supported by the National Institute of Allergy and Infectious Diseases (NIAID), The Helmsley Charitable Trust and the UC San Diego Center for Precision Computational Systems Network (PreCSN). Post credit to: Annelies Ondersma and Harrison Penrose at UC San Diego. Link to access #equipment: https://lnkd.in/g2iChuYf Contact us at: Kevin Perry [[email protected]]. Link to learn more about the Agilent #Seahorse analyzers: https://lnkd.in/gzfmrJtf #QuantitativeBiology; Salk Institute for Biological Studies, Scripps Research, La Jolla Institute for Immunology, UC San Diego, Sanford Burnham Prebys.

Join Us in #Cell-ebrating One Year of #Cutting-Edge #Cell Analysis! ?? at the UC San Diego Agilent Center of Excellence in Cellular Intelligence. Just so we order enough food, please don't forget to #RSVP(??) at the link below. ?? March 14th, 2025 ?? George Palade Laboratories, Floor 2 Lobby ? 1:00-3:00 pm We look forward to seeing you there! #FullInvite: https://lnkd.in/gXVW92tQ #RSVP at https://lnkd.in/gwWRhneU UC San Diego, Salk Institute for Biological Studies, Scripps Research, La Jolla Institute for Immunology, UC San Diego, Sanford Burnham Prebys.

The UC San Diego UC San Diego Agilent Center of Excellence in Cellular Intelligence's weekly series--#DidYouKnow--features examples of how you can push the limits of #Measurements-#Across-#Scales. This is our 18th post of this series and it is about the #Clock Within: How Macrophages Follow the #Rhythm of Time ?. #DidYouKnow that our immune system seems to respond differently at different times of the day? Turns out, even our macrophages—the #immune system’s frontline #defenders—follow a strict internal clock. ? Our macrophages synchronize their activity with our #circadian rhythm. By day, they ramp up #inflammation, primed to fight infections when we are most exposed to #pathogens. At night, they dial down immune responses, promoting #tolerance and #repair. But what happens when we disrupt this rhythm? Well, that is what UC San Diego Institute for Network Medicine (iNetMed) attempted to do. Using network-based approaches, we identified a key gene that was predicted to regulate macrophage intrinsic rhythm. CRISPR-based genetic modification (knockout, KO) of that gene showed: ?? Single-cell analysis of NFkB (an inflammatory signal) in ~600-900 cells over 4 experiments shows that KO macrophages display less Preparedness by Day – as they failed to mount a strong inflammatory (lower NFkB at 12h) response when they should have been at peak defense. They also display Higher Inflammation at Night ?? – Instead of maintaining tolerance, the KO macrophages remained hyperactive (higher NFkB at 24 h) , increasing inflammatory signals at a time when tissues should be repairing. Single-cell analysis of CREB signaling shows that KO cells display consistently high CREB signals for most of the day. Because CREB is the most potent anti-atherogenic and anti-fibrogenic molecule, KO animals appear to be protected from both diseases (not shown). This work highlights how rigorous single-cell analysis can give granular insights into how immune function is hardwired into our #biological #clocks, and that breaking this rhythm may contribute to chronic inflammation or increased susceptibility to #infections. Could targeting immune circadian pathways pave the way for better-timed immunotherapies? This work is possible because of a #Computational #Immunology Program that is supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the UC San Diego Center for Precision Computational Systems Network (PreCSN). Post credit to: Gajanan Dattatray Katkar, at UC San Diego Link to access #equipment: https://lnkd.in/g2iChuYf Contact us at: Kevin Perry [[email protected]]. Link to learn more about the BioTek Cytation: https://lnkd.in/ewYEdZ5V #QuantitativeBiology; #Rigor; #patterns; #quantification; #Immunometabolism; #immunesystem; #CircadianRhythms #Immunology #Macrophages #CRISPR #Chronomedicine Salk Institute for Biological Studies, Scripps Research, La Jolla Institute for Immunology, UC San Diego, Sanford Burnham Prebys.

UC San Diego UC San Diego HUMANOID: Center of Excellence in Human Organoid Research is getting ready to celebrate its 6-year anniversary this April 1, 2025! From a nascent #concept in 2019, to being at the leading front of a community that cares to make #organoids reliable platforms to hunt for #cures, reveal new #biology. What makes us unique? Here are some reasons, but the most #important one are the #scientists who work here. Read more about our #BioDESIGN program: https://lnkd.in/gxU2yFK4

We build #actionable #networks at UC San Diego Institute for Network Medicine (iNetMed). Here is the original #macrophage network [??link#1] and the associated concept paper [??link#2] that is now providing high-value targets to treat various diseases of the immune system: #IBD Inflammatory Bowel Disease (Colon-associated macrophages; CoLAMs), #Atherosclerosis and #MAASLD (Lipid-associated Macrophages; LAMs), and #MASH and #IPF (Scar-associated macrophages; SAMs), #Arthritis (Joint-associated macrophages; JAMs), #Cancers (Tumor-associated macrophages; TAMs), #Alzheimers (Neurodegeneration-associated macrophages; NAMs), #Circadian Irregularities (Circadian Rhythm-associated Macrophages; CRAMs) and so much more..... Link#1: https://lnkd.in/gEcMTubF Link#2: https://lnkd.in/g3UahwMq #PrecisionMedicine #NetworkMedicine #ImmuneSystem #Immunology #InnateImmuneSystem

#WeAreHiring: The #Mad, the #Brilliant, the #Fearless . At the UC San Diego Institute for Network Medicine (iNetMed), we’re not looking for the ordinary. We seek the #insanely #curious, the ones who #question everything, who #build for the #thrill of it—out of pure #passion and unrelenting #curiosity. You #push. You #attract. You spread #energy like #wildfire. You don’t just #dream of the #future—you drag others toward it. You #distort #reality, break the limits of what’s #possible, and make the #impossible seem #inevitable. You play life like a #game that only you #dare to #play. You #creep inside #minds, #crack open #ideas, and force the #world to #rethink, #reimagine, and #rebuild. In an #insane world, you are the only #sane one left. If this #resonates with you—if you feel the #pulse of #discovery in your veins—then maybe, just maybe, you belong with us. ?? Dare to push boundaries? Join us. Write with purpose to [email protected] #GeniusOrMadness #PushTheFuture #DistortReality #ReimagineEverything #NetworkMedicine #ScienceUnhinged #BreakTheLimits #OnlyTheInsane #FutureMakers UCSD Postdoctoral Association Postdoc Jobs

Thank you, Karen Steward (Technology Networks) , for featuring an important article [link below ?? ] that highlights the #hope and #hype surrounding #organoid technology and how we solve it the UC San Diego way. At UC San Diego HUMANOID: Center of Excellence in Human Organoid Research: Center of Excellence in Human Organoid Research, our #tagline—"Meet us at Phase Zero"—is more than just a #slogan. It’s a call to #action. A #challenge. An aspiration. We are reimagining drug discovery by prioritizing #reproducibility in an inherently #complex and #imprecise field. Late-stage failures in drug development are overwhelmingly expensive—we believe they should be a thing of the past. At @HUMANOID, we are #committed to #precision, not just as an #ideal but as an #imperative. Because #shaping the #future of #medicine requires nothing less. Link to article: https://lnkd.in/gxU2yFK4 Co-authors: Annelies Ondersma, Courtney Tindle, Pradipta Ghosh #Organoids #Biotech #Innovation #DrugDiscovery #TranslationalResearch #NextGenMedicine #MedicalBreakthroughs #PhaseZero #ReproducibilityMatters #FutureOfScience #HUMANOID

UC San Diego Institute for Network Medicine (iNetMed) Welcomes Its First Fulbright Scholarship Recipient: Dr. Vini Campos [Vinicius Jardim Campos] Dr. Vinicius Jardim Campos, a #gastrointestinal #surgeon from #Porto Alegre, #Brazil, has been awarded a #Fulbright Doctoral Research Scholarship to conduct research at UC San Diego’s Institute for Network Medicine (iNetMed) under the mentorship of Pradipta Ghosh. This prestigious award marks a significant milestone, making Dr. Campos the first #Fulbright Scholar at the Institute, further strengthening scientific collaboration between #Brazil and the #U.S. With a decade of experience in #clinical practice and #academia, Dr. Campos specializes in #Foregut and #Metabolic #Surgery, focusing on #esophageal diseases and #obesity. He completed his medical degree and surgical residency at Hospital de Clínicas de Porto Alegre (HCPA), where he now serves as an attending surgeon and researcher. At UC San Diego, he will contribute to the Institute's groundbreaking #research on the #immunological drivers of cell transformation in #Barrett’s esophagus and #esophageal #adenocarcinoma, expanding on their previous collaborations. About the #Fulbright #Program Established in 1946, the Fulbright Program is among the world’s most #prestigious academic exchange initiatives, fostering #scientific #excellence, global collaboration, and cultural diplomacy. Funded by the U.S. U.S. Department of State, it has supported over 400,000 #scholars across 160+ countries, including #NobelLaureates, #PulitzerPrize winners, and global #leaders. The Fulbright Doctoral Research Scholarship provides exceptional scholars with the opportunity to conduct research at leading #universities #worldwide. Recipients are selected through a highly competitive process based on academic #merit, research #potential, and their #commitment to advancing their field. This landmark collaboration between UC San Diego and #Brazil will drive new insights in #gastroenterology and #translational #medicine, reinforcing the Institute for Network Medicine’s mission to harness #interdisciplinary science for #transformative #discoveries. #FulbrightScholar #FulbrightBrazil #GlobalCollaboration #AcademicExcellence #ScientificExchange #MedicalResearch #TranslationalMedicine #BiomedicalInnovation #NetworkMedicine #PrecisionMedicine

The UC San Diego Agilent Center of Excellence in Cellular Intelligence 's bi-weekly series--#DidYouKnow--features examples of how you can push the limits of #Measurements-#Across-#Scales. This is our 16th post of this series. #DidYouKnow ?? that not all #macrophages in a population behave the same when #neutralizing #foreign threat? Reactive Oxygen Species (#ROS) play a critical role in macrophage function—neutralizing pathogens, shaping immune responses, and orchestrating tissue repair. Using single-cell ROS analysis with the ROS-ID? detection kit (Enzo), the team uncovered significant #heterogeneity in #ROS induction across macrophage populations. In control cells (#blue; WT) some cells launched rapid oxidative bursts (#reactive), while others exhibited a delayed or dampened response (#tolerance). This #variability highlights the complexity of innate immunity and underscores the challenges of population-level analysis. ?? Key Insight: However, when macrophages were genetically reprogrammed to enhance their #reactivity (#red; KO), they exhibited a uniform #early and #robust ROS burst, overcoming the natural heterogeneity observed in untreated populations. This suggests that fine-tuning macrophage responses through targeted interventions could lead to more effective immune activation strategies. ?? Why Does This Matter? In infections, boosting ROS production can enhance pathogen clearance. Excessive or prolonged ROS exposure leads to tissue damage. In chronic inflammatory diseases, controlling ROS through antioxidants or metabolic modulation (e.g., targeting NADPH oxidase) can help reduce tissue damage. Single-cell approaches provide unparalleled resolution in understanding functional diversity within immune cell populations. ?? Are you leveraging single-cell technologies to understand immune function? Share your thoughts below! If you want to know more about how BioTek Cytation C10 can help with your research, contact us at: Kevin Perry [[email protected]] or Gajanan Dattatray Katkar [[email protected]] Link to learn more about biotek-Cytation: https://lnkd.in/exmY7H2z How to #access these and other #equipment: https://lnkd.in/g2iChuYf #Immunology #Macrophages #ROS #SingleCellAnalysis #PrecisionMedicine #Biotech #EnzoLifeSciences #ResearchInnovation#training; #measurement; #biology; #quantitative; #imaging; La Jolla Institute for Immunology Scripps Research UC San Diego

The UC San Diego Agilent Center of Excellence in Cellular Intelligence 's bi-weekly series--#DidYouKnow--features examples of how you can push the limits of #Measurements-#Across-#Scales. This is our 15th post of this series. #DidYouKnow that #epithelial #morphogenesis requires a delicate balance between cell-cell #adhesion (via #junctions) and cell-#ECM interactions (via molecules such as #integrins). And if this balance is disrupted, it usually leads to epithelial reprogramming in ways to initiate almost all diseases we know (from #cancers, through #fibrosis to #diseases characterized by #inflammation). WHAT WAS DONE: Today's post (??) continues to showcase how precise measurement of growing spheroids over ~10 days reveals how a mutant protein found in #cancers weakens cell-cell #adhesion and begins to grow in the form of tubes (arrows, bottom left) and that this feature can be corrected by adding #ECM (bottom right) such that #colonies grow as control (WT) #spheroids. HeLa cells were depleted of the WT endogenous protein (by CRISPR) and then transfected to select stable colonies of cells expressing the WT and the cancer-associated mutant protein. The mutant protein displays gain-of-function by being able to bind and modulate tyrosine-phosphorylated G proteins. This finding reveals a fascinating dynamic: with weaker junctions, the mutant cells became more reliant on cell-ECM interactions to regain their architecture. These results underscore the critical role of ECM not only as a structural scaffold but also as a mediator of cellular behavior in challenging conditions. Continuous #imaging and high-throughput [#HTP] exploration of all possible combinations in 96-well mode was key to revealing the importance of #balance to achieve #homeostasis in health, and how oncogenic mutants tip the same. What to know what #oncogene, and which #signaling pathways were the culprit? Stay tuned and follow our #publications. Post credit: Suchismita Roy and Kevin Perry If you want to know more about how xCELLigence RTCA eSIGHT can help with your research, contact us at: Kevin Perry [[email protected]] Link to learn more about the eSIGHT: https://lnkd.in/gAzDis7 How to #access these and other #equipment: https://lnkd.in/g2iChuYf Need help scheduling? Kevin Perry [[email protected]]. #training; #measurement; #biology; #quantitative; #imaging; #Oncogenesis #ExtracellularMatrix #CellAdhesion #BiomedicalResearch #EpithelialMorphogenesis; La Jolla Institute for Immunology Scripps Research UC San Diego