Online tool helps advance cancer and neurodegenerative research
Researching intermolecular interaction has become easier, thanks to Isothermal titration calorimetry (ITC). However, the technology has limitations when it comes to simulating binding models, making it more difficult to study complex molecular interaction such as tau-tubulin binding. This is needed to conduct in-depth research related to cancer and neurodegenerative diseases. The EU-funded FIT (Advanced web tool for Isothermal Titration Calorimetry data analysis and management) project worked on developing an advanced ITC data analysis tool that supports researchers in elaborating and sharing new binding models. It investigated anticancer drugs known as microtubule targeting agents, focusing on the interaction of microtubule associated proteins and binding to the target. To achieve this, the project team developed online software for advanced analysis of ITC data. It studied how tau (a naturally unfolded protein) binds to microtubules and the results of this interaction, examining as well the impact of oxidative stress and zinc ions on tau binding to microtubules. Interaction of tau fragments with tubulin was studied using ITC, differential scanning fluorimetry and turbodimetry. This enabled the team to home in on fragments that were able to bind to tubulin and to extrapolate a new tau-tubulin binding model. Beyond proposing the model of tau-tubulin interaction, the team also detailed the common molecular mechanism involved in the regulation of tubulin polymerisation by microtubule associated proteins. The successful development of the web tool for data analysis enables researchers to upload raw ITC data files on the server and manage them. It also facilitates preliminary processing of raw data in addition to previewing and presenting the data in different useful ways. There are plans to make the new software tool available to other European laboratories, ultimately advancing ITC research in unprecedented ways.
Keywords
Intermolecular interaction, Isothermal titration calorimetry, FIT, microtubule targeting, tau, differential scanning