Gonzalo Aizpurua de Arteche is a PhD student at the Spanish National Cancer Research Center (CNIO), Madrid, Spain who received an EACR Travel Fellowship to visit and work at the Center for Protein Research (CPR), Copenhaguen, Denmark between February and March 2024.

The EACR, with support from Worldwide Cancer Research, provides Travel Fellowships of up to €3,500 to enable early-career cancer researchers to gain new skills through a short-term visit to a lab or research group in another country.

You can read about other Travel Fellows and their experiences here.

Name: Gonzalo Aizpurua de Arteche
Job title: PhD student
Home institute: Spanish National Cancer Research Center (CNIO), Madrid, Spain
Host institute: Center for Protein Research (CPR), Copenhaguen, Denmark
Dates of visit: February – March 2024
Research: KRAS-driven cancer affect one quarter of all human cancers. Previous experiments showed that one effector protein called RAF1 played an essential role in these cancers. Specifically, its ablation promoted lung adenocarcinomas regression. My project is now focused on understanding how this protein is regulated by studying its interaction partners. The project aims to resolve important structures which RAF1 function depends on to be able to develop drugs against these interactions. This pharmacological approach could be a promising therapy against these types of tumours.

How did you choose the host lab?

The lab from Guillermo Montoya in the Center for Protein Research is one of the leading laboratories in his field. Specifically, they possess one of the best transmision electronic microscopes in Europe. The microscope is able to resolve protein structures with a high resolution such as 2 Å. In addition, they have the experience and the perfect resources to work with purified proteins for more in vitro studies. Along with this, we had already collaborated with them and their work was one of the finest.

Can you summarise the research you did?

During my visit to Copenhaguen, thanks to all the resources that the lab has, I was able to successfully purify a complex formed by the interaction between KRAS and its main effector RAF1. This complex is formed also by another 2 chaperones (HSP90 and CDC37). We were able to take this purified complex and pre-process its structure with high resolution. Now, we are analysing the results and remodelling the complex to gain insights into the interaction between this 2 proteins. Furthermore, we purified another complex formed by RAF1 and 14-3-3 proteins. This complex was visualised in the microscope but more studies need to be done in order to obtain this structure. Strikingly, we discovered that this complex promoted RAF1 activation, a fact that was thought to be the other way around.

Gonzalo at the host lab

What were you able to do that you could not have achieved in your home lab?

This visit is giving fundamental information for my project since I was able to obtain the structure of an important interaction which is crucial for lung adenocarcinoma formation (RAF1-KRAS interaction). In my lab I could have not achieved this structure. Further insights will be obtained by analysing the structure and molecular docking will be performed in order to obtain protein-protein interaction blockers.

Was there anything you particularly liked about the host institute?

I really enjoyed working with the people in the host lab. It was a laboratory with different people from all over the world and with a lot of different cultures. I learnt a lot from them and the mood was very nice and comfortable. All of them offered me their help and were very kind to me, inviting me to their plans, chatting with me and helping me in all the experiments and throughout the experience.

Did you have a personal mentor or anyone who particularly helped you?

Yes, I had a personal mentor called Rafael. He is an expert in Cryo-EM data processing and analysing. From the first day, he offered me his help to be able to purify my protein and to use the microscope. His devotion to my project was almost as though it was his own. He was very excited with the promising results and I am looking forward to collaborating with him again.

Gonzalo and friends from the host lab

Did you take part in any interesting local activities?

One day I went to a very cool pub that had live jazz music. The mood was not only fun but very curious. In fact, we were able to listen to one of the most famous pianists in jazz improv all over the world. I enjoyed this experience a lot!

Have you brought back any specific knowledge or technique that has benefited your home lab?

I brought back a lot of knowledge from my visit. We are not a structure biology laboratory, so being there was all new for me. I learnt a lot about structure protein and electronic microscopy. Also I saw different techniques that could be very useful which I will implement in my home lab, such as HA-purifications.

Does your lab plan to do any future collaboration with the host lab?

Our plan is to come back again. In other to understand RAF1 regulation, we need to understand how and when RAF1 interacts with its partners. To this aim, more complexes formed by RAF1 and other interactors have to be resolved. Our idea is resolving as much as complexes we could to further understand how RAF1 acts and to being able to target RAF1 by different perspectives.

Want to find out more?

If you are interested in applying for the Travel Fellowship scheme, please click here for more information: EACR Travel Fellowships.