Just like lego – studying flexible protein for drug delivery #weekendusers

30-08-2018

Researchers from the Sapienza University of Rome and its spin-off company MoLiRom (Italy) are spending the weekend at the ESRF to study a protein that could potentially transport anticancer drugs.

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Ferritin is a large spherical protein (20 times bigger than haemoglobin) that stores iron within its cavity in every organism. Just like a lego playset, Ferritin assembles and disassembles. It is also naturally targeted to cancer cells. These are the reasons why Ferritin is a great candidate as a drug-transport protein to fight cancer. An international team of scientists from “Sapienza” University of Rome and the SME MoLiRom (Italy) came to the ESRF to explore a special kind of ferritin that shows promising properties. “This is an archaebacterial ferritin that have transformed into a humanised ferritin to try to tackle cancer cells”, explains Matilde Trabuco, a scientist at the Italian SME MoLiRom.

The mechanism looks simple enough: “Ferritin  has a natural attraction to cancer cells. If we  encapsulate anti-cancer drugs  inside it, it will act as a Trojan horse to go inside cells, then it will open up and deliver the drug”.

Ferritins have been widely used as scaffolds for drug-delivery and diagnostics due to their characteristic cage-like structure. Most ferritins are stable and disassemble only by a harsh pH jump that greatly limits the type of possible cargo. The humanised ferritin was engineered to combine assembly at milder conditions with specific targeting of human cancer cells.

 

Previous experiments on ID02 and BM29 had shown the team that their humanised ferritin could be triggered just by magnesium ions. The team was on ID09 last weekend tracking the different steps ferritin goes through using time-resolved wide-angle X-ray scattering, taking advantage of the newly installed stopped-flow instrument. “If we can identify, from the biological point of view, which are the critical parts responsible for opening/ closing, then we will probably be able to control the process”, explains Beatrice Vallone, professor at the Sapienza University of Rome.

The team is very hopeful of the results. They are also keen on stressing that this experiment would not have taken place if it wasn’t for X-probe, http://x-probe.org/, a training network of XFEL and synchrotron-based probes of protein structure and dynamics. This project is a Marie Sklodowska-Curie project and funded by Horizon 2020. “The three of us first met there”, explains Trabuco. “Cécile Exertier and I have just finished our PhD whilst Beatrice Vallone has provided fundamental supporton this research”, she adds. “Thanks to this network we have also met Matteo Levantino, beamline scientist and a major collaborator on this project, and Michael Wulff, beamline responsible of ID09, who have told us about the possibilities for our research on their beamline”, she adds. “This project has opened new doors in our research”.

Text and video by Montserrat Capellas Espuny

Top image: Matilde Trabuco (in red) and Cécile Exertier in the Control Cabin during the experiment.