Meet Gioele La Manno, the first ELISIR Scholar

One of the difficulties facing exceptionally talented young scientists today is the lack of positions that allow them independence early on in their research careers. PhD graduates, who want to pursue an academic career, usually have to spend years doing at one or more “postdoc(s)” – fixed-term contracts in a tenured academic’s lab – before they can get positions that allow them to run their own research groups. 

But in recent years, various US institutions such as MIT, UCSF, and Cold Spring Harbor Laboratory have begun running alternatives to traditional postdoc fellowship programs. These new fellowships allow PhD graduates with an excellent track record to have instant independence to run their own labs and undertake pioneering and innovative research early on in their career.

EPFL has now begun its own such program, called EPFL Life Sciences Independent Research (ELISIR) and run by the School of Life Sciences. The idea behind ELISIR is that nurturing top young scientists during their most creative years can usher in a new generation of leaders. The non-tenured position runs for three years with an optional renewal for another two, and offers a recent PhD graduate a full research budget, mentorship program, and the opportunity to work as independent principal investigator in an interdisciplinary institution with state-of-the-art infrastructure and core facilities.

“It has been very exciting to launch ELISIR,” says Professor Pierre Gönczy who directs the program. “There is no question that such a program responds to a need, as judged notably by the impressive quality of the young scientists who applied to the first call.”

The first call for candidates closed in spring 2018, and the first ELISIR Scholar is Dr Gioele La Manno, who has just graduated with his PhD from the Karolinska Institute in Sweden. There, La Manno worked in Stenn Linnarsson’s lab, which is known for developing various technologies for extremely sensitive and accurate detection of RNA in single cells.

One of these techniques is dubbed “RNA velocity”, which allows scientists to observe gene expression over time with unprecedented resolution. Unlike conventional single-cell RNA sequencing that only takes a “snapshot” of gene expression in a cell, RNA velocity is like “a photo captured with a long exposure, which results in motion blur”, in essence showing us not only the state of cell, but how the cell is changing over time.

La Manno developed RNA velocity during his PhD and used it to predict the future state of individual stem cells of the nervous system. His work revealed the branching lineage tree of the developing mouse hippocampus, and even examined gene transcription in the brain of the human embryo. The fruit of his labors was a superb paper that was published in August 2018. 

At EPFL, La Manno will be joining the Brain Mind Institute, from where he will interact with members of the other institutes of the School of Life Sciences to carry out cutting-edge research into the development and degeneration of neural cells.

Tell us a little about your research background.

My first important work was about how the neurons that are involved in Parkinson's disease are made. We studied this both in mouse and in humans, and we compared the two species to understand how this progression happens, and how well the mouse model matches the process in humans. 

From these data we were able to develop a machine-learning tool that automatically scores how similar a cell grown in the lab is to any of the normal brain cells. This is important for clinical trials of Parkinson's disease that aim to replace lost neurons. There you really want to know how good a cell preparation is before injecting it into patients’ brains!

What are your research plans while at EPFL?

I plan to study the retina; with my background of studying the brain, the retina felt like a natural continuation – you can really consider it as an extension of the brain. As the population grows older, we have increasing vision loss resulting from glaucoma and macular degeneration – long-lasting pathologies that involve cellular degeneration of the retina. These are very difficult to study because you can’t sample people's retinas. But something happens in the retina that makes the cells that were once stable to now lose that stability and degenerate.

How can we study the retina if we cannot access it in human tissue?

The reasoning here is that by studying the retina during embryonic development, we can understand how the cells’ stable states are reached. It is an opportunity to look at the system while it is built and stabilized. The information we gain will help us come up with ways to re-stabilize dying cells. It is like observing a building while it is being constructed: you can see the backbone and the foundation and it is therefore easier to identify future rupture points.

What made you choose EPFL?

There are many reasons, but the first is certainly the unique mixture between cutting-edge research in physical, engineering, and life sciences. Not only I enjoy the possibilities offered by this mix but I continuously strive towards making biology more quantitative and predictive; a little closer to what physics can do. But you can rarely do that with biological systems.

The second reason is prestige. The role that EPFL plays, and the faculty members, the array of people that work here – it’s great to interact with.

Surely, Switzerland is a great country to do research in; it puts in a lot of effort to make great science happen and supports the local scientific community with generous funding.

What do you find unique about the ELISIR program?

First, it’s a very innovative initiative in Europe. We were sort of missing these very early group-leader positions. I have a feeling of belonging to the European scientific community and I think there is value in the way, in Europe, we do science and we think about science. The ELISIR is a great opportunity, personally speaking, because the objective of an academic career for a researcher is, after all, to gather a team and try to develop his or her ideas. And that is my goal as well.