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Search results for "Brigitte Kieffer"

Results found for "Brigitte Kieffer"

  • Reflections on My PhD Journey: Lessons Learned

    My experience has been no different, filled with valuable lessons that I hope will inspire and guide These rotations gave me the opportunity to explore the culture of different labs, understand ongoing What ultimately made the difference was my PhD supervisor’s initiative to reach out. Different supervisors offer different styles of mentorship, but it’s crucial to find one who genuinely

  • Orthosteric Binding Experiments: How to Avoid the Most Common Data Pitfalls

    When a tracer binds two sites with different affinities, curve shape reflects the ratio of affinities Small differences produce subtle curvature; large differences produce biphasic behavior. demonstrates how premature stopping mis-ranks compounds, particularly when tracer and displacer bind at different Many programs unknowingly compare compounds measured under different kinetic biases. You may see: Early stopping → potency distortions Different stopping times → incomparable datasets Curve

  • Chemokine receptor-targeted drug discovery: progress and challenges

    Different reviews have extensively described the success and failure in drug discovery on chemokine receptors At a molecular level, different ligands bind to the same receptor and vice-versa (Marcuzzi et al. 2018 In the chemokine-receptor system, different chemokines are able to activate different pathways, which Further difficulties arise from the existence of cross-reactivity with other GPCRs and differences in Overall, the future potential lies in using different therapeutic modalities to modulate the stromal

  • From Farm Fields to GPCR Discovery, GLP-1 and GIP

    Receptor localization, ligand access, and intracellular signaling can look different in actual tissues including: Mapping where  GLP-1 and GIP receptors are expressed Observing which cell types  respond to different therapies Understanding why similar drugs perform differently in different patients These tools have

  • The Hidden Cost of Unclear Biotech Positioning

    They emphasize different elements depending on who is listening, which creates confusion instead of clarity The same company sounds different depending on the meeting , even when the science and the strategy have External stakeholders leave meetings with different interpretations of what the company actually is , positioning typically shows up in a few recurring ways: 1️⃣ Every external conversation drifts in a different on edge cases instead of the core value 5️⃣ The CEO and scientific leadership describe the company differently

  • Amylin Receptor Signaling: Three Receptors From One, and How to Profile Each

    Two compounds matched on potency can still differ in signaling bias, the degree to which each drives A ligand that favors cAMP over β-arrestin, or the reverse, can produce a meaningfully different functional Capturing these differences requires measuring both pathways in parallel, at each receptor subtype, with Each makes different demands on the receptor, and each benefits from a clear picture of subtype selectivity

  • From Snapshots to Predictions: Why Mechanism of Action Matters

    In discovery, different pathways may look identical at first glance. What happens when receptor expression is different? What happens in vivo? When Two Mechanisms Look the Same Some of the most difficult calls in pharmacology happen when two different A Case That Seemed Impossible In one real program, a compound produced four completely different assay With the right models, you’ll know (not guess) how your drug works, how it differs from others, and how

  • Profiling Immune Cell and Platelet Transcriptomes

    in transcriptomic profiling have provided new insights into the expression patterns of GPCRs across different Additionally, the study identified unique expression patterns of GPCRs in different immune cell types highlighting the robustness of the assay and the potential for cross-validation of GPCR expression across different

  • How Collaboration Drives GPCR Discoveries

    To understand how incretin receptors behave in intact tissue, Hodson needed people who saw problems differently That changed when JB’s team walked in with a different lens. The knockout behaved differently than expected. Hodson and JB’s collaboration works not because their skills align but because their thinking styles differ

  • Building Backwards: Why Top-Down Models Could Revolutionize Pain Research

    Watch Episode 170 Thinking Differently Pain research has long followed a familiar route: from molecule He also integrates concepts like sex differences , epigenetic inheritance , and neuroimmune crosstalk

  • How to Avoid the Most Common Gaps in Your Biotech Pitch

    If your pitch doesn’t immediately tell them who it’s for, why it matters, and what makes it different immediately shifts the conversation from academic interest to practical significance. 3️⃣ Why it’s different understand what sets your approach apart from existing solutions or current standards and why that difference What Changes When Your Pitch Works When your biotech pitch lands, the difference is immediate and powerful

  • Biased Agonism at the GLP-1 Receptor: A Pathway to Improved Therapeutic Outcomes

    Biased agonism is a phenomenon where different ligands acting on the same receptor trigger distinct signaling However, GLP-1R can also engage other G proteins, such as Gi/o and Gq/11, leading to different downstream Biased agonism at the GLP-1R has been extensively studied, revealing that different ligands can stabilize These differences in signaling profiles can have significant physiological implications. Cryo-electron microscopy (cryo-EM) structures of GLP-1R bound to different agonists have provided further

  • Why “Displacement” Misleads You: Allosteric Binding Demystified

    allosteric systems , adding a modulator doesn’t push another molecule off—it transforms the receptor  into a different Function: Two Different Worlds One of the most common—and dangerous—mistakes in allosteric pharmacology Allosteric Binding Is a Different Game. Learn the Rules.

  • Differential binding of Δ9-tetrahydrocannabinol derivatives to type 1 cannabinoid receptors (CB1)

    It has been proven that when different ligands bind to the receptors the effects are different depending Raïch I et al. , Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinolderivatives

  • Radioligands vs. Fluorescent Ligands: Binding Assays

    Fluorescent Probes: Differences in Binding Assays Fluorescent ligands are a type of fluorescent probes ligands can be used at a broader range of concentration without losing accuracy, as well as detect different Ease of handling is the other key difference, because fluorescent compounds do not require regulatory

  • Misread the Curve, Misjudge the Drug: Rethinking Antagonism in GPCR Pharmacology

    Terry Kenakin reframes one of pharmacology’s most foundational ideas: the difference between competitive This lecture helps you not only understand these differences, but also know when and why they matter. This is the kind of insight that makes the difference between a dead-end program and a well-informed

  • GPCR Allosteric Modulation: Why Allostery is the Engine of Drug Discovery

    This lecture is a roadmap for understanding why two drugs with similar affinity may behave completely differently Cryptic Sites, Longer Onset: Why Some Drugs Work Differently in Cells Than in Assays One of the most What If the Same Site Behaves Differently Depending on the Ligand?

  • AlphaFold’s Breakthrough in GPCR Research: Revolutionizing Discovery, Yet Awaiting Experimental Proof

    AlphaFold-predicted models revealed distinct ligand-binding site shapes, enabling the prioritization of different static structures was groundbreaking, however, GPCRs are highly dynamic proteins and continuously adopt different ligands and the cellular environment which are crucial for understanding how drugs can selectively target different

  • How System-Level GPCR Thinking Prevents Discovery Failures

    Most GPCR programs don’t fail because of weak molecules—they fail because biology behaves differently When you see the distortions baked into the system, you interpret your data differently and protect your What You’ll Gain Spot false confidence early  → Sensitivity differences can turn full agonists into partials

  • The Dr. GPCR Happy Hour Returns to Boston: September 30

    It's a short walk from the sessions, and a very different kind of evening: no agenda, no presentations A smaller gathering is the difference between meeting three people you'll actually remember and shaking

  • GPCR Selectivity Beyond the Receptor

    The consequences for coupling specificity differ across receptor systems. These differences shape how intracellular modulators behave and what their mechanistic significance reveals subcellular locations at AT1R in response to angiotensin II and the biased agonist TRV023, producing different

  • The Hidden Burn: How Internal Misalignment Drains Your Biotech’s Runway

    At first, it’s just different vocabulary. Later, it becomes different roadmaps. In reality, they’re solving different problems. You pay for both. You benefit from neither. They suffer because everyone has a different idea of what their role actually is.  

  • Molecular basis for ligand modulation of the cannabinoid CB 1 receptor

    New high-resolution structures of CB1 receptor in different functional states have significantly improved These advances have paved the way for development of novel ligands for different therapeutic applications In this review, we describe the structural determinants for modulation of CB1 receptors by different types of ligands, as well as the differences between CB1 and its homologous, the CB2 receptor.

  • β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the...

    when coupling to the same GPCR in living cells "β-arrestins mediate regulatory processes for over 800 different However, whether β-arrestin1 and 2 respond differently for binding to the same GPCR is still unknown. that the two isoforms prefer to associate with the active parathyroid hormone 1 receptor (PTH1R) in different Here, we show differences between conformational changes that are induced by P-R* or R* receptor states

  • TM5-TM6: structural switches that modulate the coupling of serotonin receptors to Gs or Gi

    What is the molecular basis that determines that GPCRs bind selectively or promiscuously to different Prior to this report we did not know how different serotonin receptor subtypes which share high sequence homology, coupled to different families of G proteins, so the comparison and structural analysis of The structural differences found between the receptor-Gs and receptor-Gi complexes evidenced that 5-HT4 These differences are mainly attributed to the characteristic Ras domain distance between Gs and Gi.

  • Ever Wondered How Drugs Are Discovered?

    You’ll explore: What makes a “discovery team” tick (and why teamwork is non-negotiable) The difference

  • VAMP2: a crucial player in the delivery of MOR to the synapse

    The t-SNARE complex is composed of two different proteins: syntaxin and SNAP-25; syntaxin is found on However, the selectivity of SNARE complex proteins to regulate the release of different types of GPCRs its bi-leucine sequence (which is considered a key element in its recycling), which can interact with different fusion proteins and also this different molecular codes will be modulated by different opioids, either endogenous or exogenous, promoving a differential organization of MOR receptors in vesicles with different

  • From Lab Logic to Leadership: How Scientific Thinking Holds Back Biotech Operations

    Startups Play by Different Rules — and Most Scientific Founders Miss That   A research lab is designed And that difference changes everything. 👉 Scientific thinking values thoroughness, error reduction, Startups demand something different: ✅ Clarity of direction even when the picture is incomplete.

  • How a Failed Experiment Created a Powerful GPCR Imaging Tool

    Instead of abandoning the compound, the team did something different: they looked at what it could do It happened because Hodson and JB thought differently — and allowed the clash of disciplines to be productive

  • Orthosteric vs. Allosteric Interactions: The Silent Decider of Safety and Success

    The difference between orthosteric vs. allosteric mechanisms isn’t just academic — an orthosteric antagonist Allosteric sites operate differently: ligands bind elsewhere, transmit energy changes, and shift the That perspective helps explain why two compounds with similar affinities can deliver very different clinical

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