GENIO italiano Giuseppe Cotellessa

 Antibody Development /  Sviluppo di anticorpi Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa Once the developability assessment hurdles are cleared, your antibody candidate moves into broader development.  The emphasis during this phase is on understanding “the good and the bad” of how it will behave in the human body. Clearly, the pharmacological profile of antibody therapeutics differs significantly from that of small molecules.  A lot of this stems from the profound difference in molecular weight: antibodies are approximately 300 times larger, with a molecular weight of ~150 kDa compared to less than 500 Da for small molecules. Another important difference is the connection between pharmacokinetics (how an organism affects a drug) and pharmacodynamics (how the drug affects the organism).  With small molecule drugs, these two phenomena can be discreet.  With mAbs, they’re interconnected. Pharmacokinetics (PK) and Pharmacodynamics (PD) As protein thera

 Antibody Glycosylation /  Glicosilazione anticorpale Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa A Critical PTM with Enormous Drug Development Significance. Antibody glycosylation is another critical consideration for developing and optimizing a therapeutic candidate, and one that can lead to downstream consternation if overlooked. Glycans, or carbohydrate molecules covalently appended to other biomolecules, are a common class of protein PTM, which have a wide variety of important roles in biological systems and mechanisms. The main challenge with glycan structures is that their biosynthesis is not template driven, like it is with DNA, RNA, and proteins.  This results in high heterogeneity in glycan structures. An individual protein can have a wide number of glycoforms—varying only by glycosylation—when expressed in the same cellular system at the same time.  Glycoforms can differ from one another with respect to different glycan structures occurring

 Antibody Optimization /  Ottimizzazione degli anticorpi Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa Following the identification of leads from antibody discovery, optimization of these leads may be necessary to explore, in a more targeted way, if increases in affinity and potency can be achieved. A similar process, called affinity maturation, happens naturally during an immune response. The immune system uses somatic hypermutation (as well as class switching, for example, from IgM to IgG) in a cellular process to increase the diversity of antigen-specific antibody CDRs and increase the immune response thereby adapting to new foreign threats during the lifetime of an organism, eg., microbial infection. This is then followed by antigen binding, similar to that used in the display technologies described in previous sections. The process occurs over weeks following an infection, either acute or chronic, or vaccination. In the germinal centers, antibody-p

 THE FUTURE OF QA/QC IN METABOLOMICS: NOTES FROM REGULATORY TOXICOLOGY /  IL FUTURO DEL QA/QC IN METABOLOMICA: NOTE SULLA NORMATIVA DALLA TOSSICOLOGIA  Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa “One of the challenges is, how do you actually bring the community forward as a whole? How do you encourage them?” –Mark Viant, University of Birmingham, UK Experts in the metabolomics and lipidomics communities believe that clear quality assurance and quality control (QA/QC) guidelines are necessary.  In 2007, the Metabolomics Standards Initiative published a series of papers outlining a set of standards and guidelines.  Now, many agree that researchers should update these standards, develop more rigorous guidelines, and take steps to improve their adoption within the community.2,3 Groups involved in this process include the Metabolomics Society, the Metabolomics Quality Assurance and Quality Control Consortium (mQACC), the Lipidomics Standards Initiative, an

BEST PRACTICES FOR VACCINE RESEARCH /  BUONE PRATICHE PER LA RICERCA DEI VACCINI Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa Vaccination is largely recognized as the most cost-effective way to fight human infectious diseases.  Vaccines play a vital role in immunization strategies that have contributed to eradicate dangerous pathogens, increase human life expectancy and reduce disabilities & suffering all around the world.  Because both prophylactic and therapeutic vaccination can help reach herd immunity, vaccine research will be crucial in maintaining public health in the future.  The majority of vaccine studies still rely on the use of animal models, in which animals are immunized with the candidate vaccine and then exposed to the pathogen of interest.  Most often, the efficiency of the vaccine candidate is assessed with the help of molecular biology techniques that require the homogenization of the infected animal tissues.  Bertin has developed

 Highly Sensitive Methylation Detection Using Enzymatic Methyl-seq and Twist Target Enrichment /  Rilevamento della metilazione altamente sensibile utilizzando metil-seq enzimatico ed arricchimento del target di torsione. Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa Figure 1. Methylation Conversion. Methylation sequencing involves enzymatic or chemical methods of converting unmethylated cytosines to uracil through deamination, while leaving methylated cytosines intact. During amplification, uracil is paired with adenine on the complementary strand, leading to the inclusion of thymine in the original position of the unmethylated cytosine. The end product is asymmetric, yielding two different double stranded DNA molecules after conversion (top row); the same process for methylated DNA leads to yet additional sets of sequences (bottom row).  / Conversione di metilazione. Il sequenziamento della metilazione implica metodi enzimatici o chimici per convertir

 Rodents, Llamas, Sharks, Chickens, and Cows, Oh My! /  Roditori, lama, squali, polli e mucche, oh mio! Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa Biomedical research and drug discovery have relied pretty heavily on mouse, rat and rabbit model systems, both for pre-clinical research and drug discovery. But with the recent approval of Cablivi (caplacizumab), a heavy-chain only, single-variable domain “nanobody” initially found in llamas and other camelids, many companies and researchers are focusing on discovery and development of these “small” biologics. Nanobodies are 12–30 kDa, more than five times smaller than full-length murine and human monoclonal antibodies.  Like other antibodies, nanobodies are modular, yet their size gives them greater stability, flexibility in the routes of administration, less potential for immunogenicity and greater manufacturability. Their size also gives them greater accessibility to different antigens, unlocking the do