IBBR Seminar Series
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.
Life of biological molecules spans time and length scales relevant at atomic to cellular time and length scales. Hence, novel molecular modeling approaches are required to be inherently multiscale. Here we describe multiple methodologies developed in our laboratory: rapid discrete molecular dynamics simulation algorithm, protein design and structural refinement tools. Using these methodologies, we describe therapeutic strategies to combat this HIV and cancer, as well as design novel approaches for controlling proteins in living cells and organisms.