You're the first author on "An atlas of human kinase regulation" \cite{Ochoa_2016}. This seems like a massive research effort to catalog kinase regulation. What lead to the idea and how did you accomplish the research?
The idea behind this project was to learn how human cells elaborate decisions and ultimately trigger responses that make them adaptable to changing environments. One of the fastest mechanisms by which cells can modulate their internal processes is kinase regulation. Kinases are enzymatic proteins capable of governing cascades of events happening inside the cells within a few seconds. In fact, deregulation of kinases is very often associated with cancer and disease. However, our understanding of kinase regulation has always been limited to the simultaneous study of a few kinases. In this project, we have collected 42 parallel mass spectrometry studies quantifying close to 3 million events. By crowdsourcing all this data from the community, we were able for the first time to have a general view of how half of the known kinases take coordinated decisions across a large panel of perturbations.
What was the key finding of the paper? Where there any surprises along the way?
One of the most relevant findings is the indication that kinase regulation profiles can be used as a barcode to distinguish specific responses occurring in human cells. In other words, if we perturbed the cellular environment in a similar way, the same specific pattern of responses is activated inside the cells. The profiling of the kinase regulatory status opens multiple possibilities. For instance, someone can start wondering which drugs activate a similar pattern of kinases as an already approved drug. Instead, someone might also try to revert or engineer different internal processes keeping track of the resulting kinase activation barcode.
Additionally, we also discovered that the profile of kinase regulation across perturbations is useful to search for other molecules that might be responsible for the cellular response. This indicates a fundamental link between who takes the decisions and who executes them inside human cells.
I sincerely think many surprises on this research are still to come. To take full advantage of our research, we developed
phosfate.com a web interface where people can reanalyze their own signaling data, compare it with the compiled atlas and discover new insights on the regulatory events relevant to their own research.
What are you working on now?
Our understanding of human signaling is still very limited. During my postdoc at
Pedro Beltrao’s lab at
EMBL-EBI, I’ve focused on disentangling the basis of the signaling events determining the human decision-making using the myriad of data available nowadays. What are the most relevant events, which players determine the outcome of the cell or how we can influence the master regulators in order to redirect the cellular outcomes are some of the most relevant pending scientific questions I would like to answer.
Was there a key reason why you decided to write your article on Authorea? What were some of the features you liked?
This work is a collaboration between our lab based in Cambridge (UK), Silvia Santos’ lab in London (UK), Judit Villén’s lab in Seattle (WA) and Athanasios Typas’ lab in Heidelberg (Germany). With people collaborating in 4 different locations, we required a platform that would allow us to simultaneously access the same document in a visually friendly interface and take advantage of the low-level Markdown/LaTeX editing. Authorea worked perfectly, some authors could edit the document in the website without knowing they were contributing to a LaTeX compiled document. Additionally, the manuscript was hooked to the same Github project where all the data analysis code was hosted. But the true benefits of using Authorea came when formatting the manuscripts for publication. Both the
BiorXiv preprint as well as the peer-reviewed article finally published in
Molecular Systems Biology went from live editing to publication-ready documents in the fraction of a second. I look forward to future improvements in Authorea. A distraction free mode for writing would be great!