A group of NIH supported investigators requests funding to purchase an isothermal titration calorimeter (ITC). The instrument will be used to probe the thermodynamics of protein and nucleic acid complexes involved in a number of important biological processes and diseases, including among others: microRNA biogenesis, embryogenesis, bacterial pathogenesis, amyloid formation, trichomoniasis, Alzheimer's disease, cancer and gene expression. The microcalorimeter will be located in the UCLA-DOE Biochemistry Facility where it will be accessible to the entire UCLA research community. This unique technology is a label-free, rapid and reliable means to obtain thermodynamic information about complex formation. The information obtained includes the binding stoichiometry, affinity, enthalpy and entropy. Access to this technology is lacking at UCLA as the campus contains only a single older-generation microcalorimeter whose access by UCLA scientists is limited. The specific instrument we are requesting is an iTC200 produced by MicroCal, Inc. (Northhampton, MA). It represents the state-of-the-art in ITC technology and has unparalleled sensitivity that enables experiments to be performed with up to 7-fold less material as compared to older-generation instruments. The iTC200 is also capable of measuring a broad range of interactions with sub-micromolar to nanomolar dissociation constants. Thus, it is well suited to serve the needs of the broad user community at UCLA. An experienced Ph.D.-level staff member with salary support from UCLA will be responsible for operating and maintaining the instrument. UCLA will also provide funds to service the instrument, which combined with an effective recharge system, will ensure that the microcalorimeter is productively used.
|Sjodt, Megan; Macdonald, Ramsay; Spirig, Thomas et al. (2016) The PRE-Derived NMR Model of the 38.8-kDa Tri-Domain IsdH Protein from Staphylococcus aureus Suggests That It Adaptively Recognizes Human Hemoglobin. J Mol Biol 428:1107-29|