Emergence of Adaptive Immunity: The Answer to Everything
IBBR Seminar Series
Cytokines are typically single gene products that potently modify immune responses. IL-12 and IL-23 are among the exceptions to this paradigm, since they are heterodimers expressed from distinct genetic loci. Typically, activated innate cells co-express both subunits simultaneously and secrete a fully active heterodimeric cytokine which then drives IFNγ or IL-17 production by T cells.
Glycans are complex molecules with different carbohydrate subunits, linkage stereochemistries, and branching patterns; all of which play a role in their biological functions. Hydrogen / deuterium exchange–mass spectrometry (HDX-MS) has become a standard method for analyzing conformations and binding interactions of solvated proteins. Carbohydrates, model systems for glycans, are susceptible to HDX since they contain labile hydrogens, primarily in the form of hydroxyls, which can be labeled with deuterium (D) upon exposure to deuterated solvents.
At weddings, the bridal photo is taken under bright lights, with the happy couple holding still. Traditionally in science, the “best” observations are those with the largest signal from the most tightly controlled system. Like bridal photos, the results are not always exciting. In a wide range of phenomena – the dance of proteins in function, femtosecond breaking of molecular bonds, the gestation of fetuses – tight control is neither possible, nor desirable.
Protein structural models are useful in a variety of applications. However, not all structures are solved
with a degree of accuracy that makes them suitable for use. And surprisingly, even in “good”
structures, not all regions are accurately solved. Interpreting from unreliable models - or unreliable
regions - yields unreliable results, and models with major structural defects may behave unpredictably
in computational applications. Some form of quality assurance is necessary.
For years, efficient and targeted delivery of oligonucleotides has been recognized as the #1 challenge for the development of this new class of therapeutics. While GalNAc has been extremely successful recently it only address the delivery in Hepatocytes. For decades people have tried to use all sort of peptide and nanoparticle systems. Only one is currently approved as commercial drug: ONPATTRO™ [Alnylam]. We will present different approaches, the pros and cons, and the challenges still to be solved.
Abstract: Nucleic acid vaccines are emerging alternatives for the prevention and treatment of infectious diseases as well as for pathologies such as cancer, allergies, autoimmune diseases, and drug dependencies. These vaccines induce the expression of encoded antigenic/therapeutic proteins or peptides (e.g., derived from a pathogen, a human self-protein, or a malignant neoplasm) in the body of an immunized (vaccinated) subject, and elicit adaptive immune responses, including humoral and cellular immune responses, as well as activate innate immune responses.