Ribosome Newsletter: Navigating the Convergence of Proteomics, AI, Synthetic Biology, and Translational Medicine
Welcome to this week's edition of Ribosome. In this issue, we delve into a range of innovative research from the mapping of functional lysines on living cell surfaces, which holds promise for drug target discovery, to the impact of phosphorylation-site mutations on protein-protein interactions in disease pathways. We also spotlight significant market movements, including the predicted surge in the mass spectrometry market and the rapid expansion of the global protein expression market. Plus, don't miss our feature on Roche's latest FDA breakthrough designation for an Alzheimer’s blood test, a development that could transform early diagnostics. Stay informed with Ribosome, where science meets strategy.
Proteomics Innovations
Researchers developed a novel chemical proteomic probe, OPA-S-S-alkyne, designed to selectively target and label lysines on the surfaces of living cells. This probe facilitated a comprehensive chemical proteomics strategy, termed global analysis of surface functionality (GASF), enabling the mapping of 2639 lysine sites on HeLa cell surfaces—the largest dataset of its kind. Hyper-reactive lysines identified on key proteins, such as ROR2 and Endoglin, were validated through structural analysis, underscoring their potential as critical interfaces in protein complexes and therapeutic targets. This groundbreaking approach not only enhances our understanding of cell surface dynamics but also opens new avenues for drug discovery targeting membrane proteins.
Recent research has systematically investigated the role of autophagy in neurons by using integrated proteomics, highlighting how this process targets various cellular components for degradation, crucial for maintaining neuronal health. The study identified that autophagy in neurons significantly involves the selective degradation of the PKA-RI complex, a critical regulator of neuronal activity, mediated by the autophagy receptor AKAP11. Disruption in the interaction between AKAP11 and PKA-RI complex leads to an abnormal accumulation of this complex, impacting the homeostatic mechanisms within the neurons. Furthermore, the research demonstrated that enhancing the autophagic activity could be a potential therapeutic strategy to mitigate neurodevelopmental and neurodegenerative disorders by restoring the balance of critical neuronal proteins.
Recent research investigated how mutations in human phosphorylation sites within intrinsically disordered regions (IDRs) of proteins influence protein-protein interactions, crucial for understanding disease mechanisms. The study utilized peptide-based interaction proteomics to analyze 36 disease-associated mutations affecting phosphorylation sites. Results highlighted significant differences in the interactomes between phosphorylated and non-phosphorylated peptides. A specific focus was placed on a serine phosphorylation site mutation in GATAD1, linked to dilated cardiomyopathy, which disrupts its interaction with 14-3-3 family proteins, affecting GATAD1's nucleocytoplasmic transport by masking a nuclear localization signal. This comprehensive analysis underscores the critical role of phosphorylation in mediating protein interactions and the potential impact of mutations on disease pathology.
Therapeutic Applications
A study assessed the effectiveness of the RAS(ON) multi-selective inhibitor RMC-7977 across various pancreatic ductal adenocarcinoma (PDAC) models, revealing significant anti-tumor activity and improved survival rates. The inhibitor specifically targeted the active forms of KRAS, HRAS, and NRAS, showing pronounced anti-tumor effects at safe exposure levels while normal tissues experienced only temporary reductions in proliferation without apoptosis. However, treatment resistance emerged, linked to Myc copy number gains in relapsed tumors; this resistance was potentially mitigable through combined TEAD inhibition, suggesting a promising strategy for enhancing therapeutic outcomes against PDAC.
领英推荐
A recent study revealed that ITPRIPL1 acts as an inhibitory ligand for CD3ε, playing a significant role in hindering T cell activation within the tumor microenvironment. This interaction between ITPRIPL1 and CD3ε disrupts critical signaling processes, such as calcium influx and ZAP70 phosphorylation, which are essential for the initial activation of T cells. Utilizing a neutralizing antibody against ITPRIPL1 not only curbed tumor growth but also increased T cell infiltration in various solid tumor models in mice. This finding suggests that targeting ITPRIPL1 could be a promising strategy to enhance the efficacy of cancer immunotherapies across multiple tumor types.
A comprehensive proteogenomic and metabolomic analysis was performed on 102 Chinese patients with papillary thyroid cancer (PTC), classified by different recurrence risks. Key findings include the identification of mutations in MUC16 and TERT promoters and various gene fusions like NCOA4-RET, particularly enriched in high-risk categories. The study established four PTC subtypes with distinct molecular, metabolic, and immune profiles significantly influencing recurrence risks and prognosis. These insights not only enhance our understanding of the molecular underpinnings of PTC recurrences but also facilitate precision medicine approaches for treatment and early diagnosis.
Industry Updates
The global mass spectrometry market is forecasted to grow from $6.3 billion in 2023 to $15.5 billion by 2034, marking a robust CAGR of 8.5%. This growth is driven by technological advancements, increased emphasis on diagnostic procedures for various cancers, a rise in chronic diseases, and heightened research and development activities. Key players such as Waters Corporation, Kore Technology, and Danaher Corporation are leading the charge with innovative product launches and strategic mergers and acquisitions.
The Global Protein Expression Market is on track for rapid expansion, expected to grow from USD 3.3 billion in 2023 to USD 13.7 billion by 2034, achieving a CAGR of 13.7%. This growth is driven by the rising demand for protein-based therapeutics, increased R&D investment from biopharmaceutical giants, and the growing emphasis on personalized medicine. North America dominates the market due to robust R&D funding and healthcare infrastructure, while the Asia Pacific region is anticipated to experience the fastest growth due to advances in proteomics and genomics research.
Roche has secured a breakthrough device designation from the FDA for its Elecsys pTau217 blood test, aimed at enhancing early diagnosis of Alzheimer’s disease. This test identifies amyloid pathology, a key marker of Alzheimer's, potentially transforming the diagnosis process and improving access to appropriate care and clinical trials. This designation will accelerate the regulatory review process, paving the way for quicker access to this diagnostic tool.
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#proteomics #biomarkers #ai #decadeofproteomics #translationalmedicine #syntheticbiology
Experimental Medicine , Faculty of Medicine, UBC, Vancouver | Medical Content Writing
1 个月How can collaboration between proteomics, AI, synthetic biology, and translational research drive innovation in the life sciences industry? https://lnkd.in/guWiXGVC
Innovator, Director, Writer, Designer
7 个月The Metabolic Disorders Solve Programme We see that metabolic disorders are an epidemic in the world." Your Health Is In Your Mouth” (Book) can be found on Google “The book provides comprehensive information on the topics of saliva its functions and its natural cure.
Innovator, Director, Writer, Designer
7 个月Metabolic Disorders Solve Programme We see that metabolic disorders are an epidemic in the world. All Allopathic, Ayurveda, Homeopathic, colour path, Iso path, naturopathy, Antipathy, Zyso pathy, Bio-chemic- path, fruit path, vitamin path, home path, acupressure path, acupuncture path, spiritual path, rake path electro-homoeopath, leaf path, flower path, Unani, Siddha, and Every country have Indigenous systems of medicine, Traditional systems of medicine but all are failed to cure diabetes and metabolic disorders. ?We see that all kinds of metabolic disorders take place due to mutations of enzymes, lipids, and any food we eat which means we are not eating properly as required for digestion and mixing all enzymes. To solve this problem I wrote a Book (English) “Your Health Is In Your Mouth” (Hindi) “Aap Ka Sawasth Aap Ke Muh Me” You can find it in a Google search. "The book provides comprehensive information on the topics of eating, digestion system, saliva, and enzymes."