Recap of MicroCal User Days in San Diego and Cambridge
by Verna Frasca,Wednesday, 9th November 2016
I always enjoy meeting our Malvern customers whenever I travel to different sites and events. I have been assisting customers with MicroCal ITC (Isothermal Titration Calorimetry) and DSC (Differential Scanning Calorimetry) instruments for over 15 years, and there are customers I have known since 2001. Every time I think I “know it all” I always learn something new from our customers, such as a unique sample analyzed using our instruments, or a “trick” for sample preparation or data analysis.
Muneera Beach and Verna Frasca
Malvern Instruments recently hosted two MicroCal “User Days” in San Diego, CA (October 18), and Cambridge MA (October 27). Each event was attended by about 50 scientists, as well as several Malvern team members. The User Days included presentations by regional scientists, on how MicroCal ITC and/or DSC contributed to solving problems in their research. There were also presentations by Malvern scientists, and round-table discussions. The meetings also allowed scientists to network with other local MicroCal users, and reconnect with former colleagues.
It was a pleasure to participate in these meetings and spend time with scientists who use our instruments, including several customers I have known for a very long time. Everyone who attended took home new information to their lab and colleagues. Thanks to all the User Days organizers, speakers, participants, and the staff at the venues (The Alexandria at Torrey Pines, San Diego, and the Boston Marriott in Cambridge, MA).
The speakers at the West Coast Users Day meeting in San Diego included:
William Callahan (Amgen): “Amorphous Suspensions of a Model Protein”
Dr. Callahan discussed the feasibility of using amorphous protein suspensions for biopharmaceutical formulations, rather than high concentration formulations. DSC was used to characterize suspensions of different monoclonal antibodies, and compare thermal stability of suspensions and liquid formulations.
Matthew McGann (Malvern Instruments): “Assessing Bioformulation Stability – From Prediction to Particle Count”
Dr. McGann discussed how Malvern instrumentation (including Zetasizer Nano, Viscosizer, OMNISEC, MicroCal DSC, Nanosight, Archimedes, and Morphologi G3-ID) are used together to characterize critical quality attributes of biopharmaceutical products, such as stability, aggregation, and particle size.
Dr. Ozorowski described how DSC is useful in characterizing and screening mutants and new constructs of HIV-1 Env, the only antigen available on the surface of the HIV virus. These new mutants and constructs can result in more well behaved immunogens, which can then be used for vaccine development.
Dr. Bobkov is the director of the Protein Production and Analysis facility, and he gave an overview of Isothermal Titration Calorimetry (ITC), experimental design, troubleshooting, and tips on publishing ITC data.
Mr. Gandhi discussed how DSC, light scattering, Raman, and other technologies are used to characterize ADCs (antibody-drug conjugates) and their formulations.
I presented a review of how ITC is used to characterize epigenetic proteins (including readers, erasers and writers) interacting with histones and DNA, to study how these interactions work, and help discover and develop new drugs.
Dr. Beach summarized how ITC is used as a label-free enzyme kinetics assay, as a replacement for more traditional spectroscopic or discontinuous enzyme assays.
The talks at the New England Users Day in Cambridge on October 27 included:
Aditi Soni (Novartis Institutes for Biomolecular Research): “Drug Delivery Using Cyclodextrin Solubilization”
Ms. Soni described how ITC provided insights into the design of small molecule drug delivery systems using cyclodextrin, and how the drug interacted with cyclodextrin in a variety of experimental conditions.
Frank Bruzzese (Takeda Pharmaceuticals): “Idiosyncrasies of Substrate Binding to the Canonical and Non-canonical E1 Enzymes Revealed Through ITC”
Mr. Bruzzese discussed how ITC revealed the different mechanisms of these classes of enzymes, and how that information can make decisions in drug discovery.
Jonathon Rodenfels (Yale University): “The Energetic cost and Efficiency of Early Vertebrate Development Conjugates”
Using early zebrafish cleavage stage embryos as a model system, Dr. Rodenfel’s lab used a MicroCal VP-ITC to directly measure the heat dissipation rate of the embryos during early cell cycles, and compared to oxygen consumption rate (RO2) of embryos in vivo. The heat dissipation rate oscillations from ITC correlated with the embryonic cell cycle and matched its period. These results provided understanding the energetic economy of early vertebrate embryogenesis and how it is connected to the rate of embryonic cell divisions.
Dr. Wilcox discussed how ITC and DSC can be used to characterize interactions involving metal ions, including metal binding proteins, and the special considerations involved in these studies.
Deborah Pheasant (MIT): “Notes from a Calorimeter Maître d’”
Ms. Pheasant provided tips for designing and running ITC and DSC experiments, based on her experience managing the Biophysical Instrumentation Facility at MIT, and training ITC and DSC users.
James Kranz (Shire): “Protein Thermal Stability and Ligand Binding: DSC, DSF and Thermal Shift Analysis in Pharmaceuticals”
Dr. Kranz discussed how thermal stability assays such as DSC and DSF are used to measure the affinity between small molecule drugs and target proteins, using the shift of Tm. Thermal stability assays such as DSC are also useful in characterization of protein formulation development, and minimization of aggregation.
Verna Frasca (Malvern Instruments): “Microcalorimetry by Design: ITC and DSC for Life Sciences Research and Drug Discovery and Development”
I provided an overview of how ITC and DSC work, and some applications on the use of microcalorimetry in life sciences and drug discovery and development.
