The Alliance currently focuses its efforts on Collaboration, Training and Exchange. It is dedicated to fostering cross-institutional knowledge transfer, enabling high risk projects, promoting exchange of staff and collaboration, sharing expertise, and offering training and education to members of the research community. Click on the links above to view our latest activities.
Mid Year Update 2018
Heidelberg, July 2018
At the halfway point in 2018, we thought we would take the opportunity to look back at what we have achieved over the past year and summarize our objectives for the remaining months.
Check out our newsletter to see what we have been up to.
Highlights include the 2nd Personalized Health Conference last November at Stanford, the first Bridging Excellence Seminar give by Prof. Andrew Fire at EMBL, and the confirmation from 33 group leaders across EMBL and Stanford that they would like to join us as members.
Over the next few months we will be working on the website to provide more detail on the new members, and the exciting collaborations that they have proposed. We will also be working to secure funding for our full program of activities and organizing the 3rd Personalized Health Conference to be hosted at EMBL from 13-16th November 2019.
Keep up to date via the website or follow us on twitter @LiSciAlliance
Ulla Gerling-Driessen (Bertozzi Lab, Stanford) and Will Mueller (Steinmetz Group, EMBL).
NGLY1 deficiency: An interview with Will Mueller & Ulla Gerling-Driessen
The Grace Science Foundation (GSF) was established to find, recruit, and fund a diverse team of researches across the globe to study a condition known as N -Glycanase 1 (NGLY1) deficiency. This is a rare disease that currently affects 47 patients worldwide. GSF has recruited five groups from EMBL and Stanford to be part of the worldwide team of researchers studying NGLY1 deficiency with expertise in various aspects of biology. Scientists from the Steinmetz Group at EMBL and the Bertozzi Group at Stanford are part of the research team. We caught up with two postdocs, Will Mueller (EMBL) and Ulla Gerling-Driessen (Stanford), to learn about the NGLY1 project, get their tips on effective collaboration, and what lessons they’ll take with them in the next phase of their careers.
Tell us about the project that you're both working on.
Will: NGLY1 deficiency is caused by mutations in the NGLY1 gene that result in a loss of function. Although the function of the gene was known, it wasn’t clear how mutations in this gene could cause disease. Our lab was involved in multiomic profiling to look at cell-wide changes in the gene-to-protein pipeline and see what happens when you lose NGLY1. The Bertozzi Group looked into some of the hits we found, and identified one of the targets of NGLY1.
Ulla: We were able to link the activity of NGLY1 to the transcription factor Nrf1. It turns out that NRF1 is activated via a very unconventional pathway – the ERAD pathway – in which NGLY1 is a key player. The main function of Nrf1 is maintenance of the proteasome, which is particularly important under conditions of cellular stress.
The functions of Nrf1 are very diverse: it’s involved in the cell’s antioxidant response, in proteasome function, embryonic development and particularly neuron development. By establishing this causal relationship, we were able to explain some of the diverse symptoms of NGLY1 deficiency, which until then were not well understood.
How has this project benefitted from a collaborative approach?
Will: The expertise of Ulla and the Bertozzi Group allowed us to work together to draw better conclusions from our data. Without Ulla’s work, the relevance and context of the gene profile we saw wouldn’t have made much sense. Now the Bertozzi Group is following up on Nrf1 as a potential therapeutic target, not only for NGLY1 deficiency but also for other diseases.
Ulla: It’s important to say that it was not just us and EMBL. There’s a team and a lot of people involved who all have the same aim of finding a treatment and understanding the disease. They all look at it from a different angle and from that we can we can build an overall understanding of the disease.
It’s been an incredibly wonderful thing to say, “This is cool, but I don’t know what it means. I could Google it, or I could send an email to this team of people and get some wonderful suggestions and responses.”
How do you think you have personally benefitted from this project?
Will: The contacts that we’ve made are great and have made my work easier. It’s been an incredibly wonderful thing to say, “This is cool, but I don’t know what it means. I could Google it, or I could send an email to this team of people and get some wonderful suggestions and responses.” So it’s the realest ‘two minds are better than one’ experience that I’ve ever had.
Ulla: I met a great person! (She means Will). It’s also given me an introduction to EMBL, which is somewhere I would be excited about carrying on my research in the future. I think the collaborative environment at EMBL reflects the benefits that we also experience with the NGLY1 project.
What have you learned from this collaboration that you'll take with you to your next positions?
Ulla: This project made it very clear to me that when you’re answering an important question, you can’t do it alone. You need collaboration. In the best-case scenario, you need people with expertise in different areas and then you need to bring together that knowledge.
Will: Delegation. How you divide things up and get everyone to participate in the process helps people take ownership. If you have a lot of people contributing to specific aspects of the project, it gives them purpose and a sense of direction. Also, face-to-face contact is essential. If that’s not an option then Skype as much as possible – don’t just send emails. It’s absolutely essential to have a personal connection as well as a scientific one.
"Nobody can be an expert in everything. Combining expertise in different areas is the best way to answer a big question or work on a challenging project."
The Life Science Alliance offers joint postdoc positions between EMBL and Stanford. Why should other researchers consider taking on a collaborative project?
Will: Because you never know where it’s going to lead or what possibilities the other person’s expertise will open up – either for the project or yourself.
Ulla: Nobody can be an expert in everything. Combining expertise in different areas is the best way to answer a big question or work on a challenging project.
If you would like to donate to the Grace Science Foundation, you can do so via https://gracescience.org/donate/
“We want to put all of the tools in the hands of the scientists who are doing the research.”
Interview with Susan Holmes & Wolfgang Huber
Susan Holmes, Professor of Statistics at Stanford University, recently came to EMBL to give a talk in the Distinguished Visitor Lecture series. We took this opportunity to speak to Susan and EMBL group leader Wolfgang Huber about their joint research and the benefits of a Stanford-EMBL collaboration.
Susan, tell us a bit about your research focus.
I’m interested in solving real biology problems. I like to provide tools for scientists to analyse their own data, and to make it easier for them to do it right. So, if they have the tools, it empowers them to do their own thing and we can guide them with tutorials and documentation, which saves everybody’s time. A long time ago, we started with microarrays; now there’s high-throughput sequencing. From the point of view of a statistician, a lot of what comes up is variations on a theme. Biologists sometimes think, “I only want to learn the methods to analyse this one type of data,” but they don’t realise that that specific type of technology will be out of date in two or three years, so they’re better off learning the basic principles of filtering, normalisation, renorminalisation, visualisation, and so on. So those are the variations on a theme.
How has your collaboration with EMBL and Wolfgang Huber developed?
I met Wolfgang in the early 2000s. We’re both interested in reproducible research tools, so that was a common denominator. All of my collaborations have a lot to do with either the immune system or the microbiome, so my group made a package for the Bioconductor project that would help people analyse microbiome data. Wolfgang was involved in leading Bioconductor so that’s how we got talking.
We also started working on a book around 5 years ago, this has been a moving target because the technologies – especially the computational ones - were changing so fast. Now we’ve finished it: Modern Statistics for Modern Biology, and we’re continuing to make material online and teach courses together at Stanford. We’ve never written a paper together but we have collaborated a lot through students.
"To have interactions -like short stays- that are more than just conference visits, but less intensive than moving your whole life – this is very fruitful."
What is the major benefit of a Stanford-EMBL Alliance?
Wolfgang: For people who are in training, it’s the ability to have different labs from quite different environments to talk to. To have interactions -like short stays- that are more than just conference visits, but less intensive than moving your whole life – this is very fruitful. You can do a project somewhere for six weeks and get new experiences that way.
Susan: Very often – and this is mostly true for undergraduates – students can’t make a decision about what they want to do. But if they try something out during a short-term internship, they can decide, “Oh, I can see myself thriving in this environment,” or, “I don’t like this at all.” If you go for two months, it’s not the same commitment, it’s not so high risk, and I think that helps.
What is unique about the Stanford-EMBL alliance?
Susan: At Stanford, scientists tend to work much more independently. It’s much less collaborative in the sense of infrastructure. Sometimes, as PIs at Stanford become more senior, groups become bloated with multiple layers. It’s not very dynamic for the personnel, because they don’t have direct access to PI’s any more, so it’s sort of better here.
Wolfgang: Technologically there are a lot of overlaps. In some things Stanford is more advanced, in others, EMBL has great resources like the databases hosted by EMBL-EBI. We also have this great system with relatively small, early-career groups who are supported by our core facilities. A group leader wouldn’t normally be able to do the same things by working alone.
"So the whole idea of our approach is to make tools to put in the hands of the biologists. We’re saying, “we want to teach you.” Nothing should be a black box."
What are your future plans for this collaboration?
Susan: We obviously have a lot of overlap. What I see as the future of biology is this systems approach where you look at multiple things at the same time – for example, a person’s immune system plus the microbiome and the transcriptomics – so you have multi-modalities. I think all of us are developing methods and resources for doing that. We try to make our statistical methods applicable to heterogeneous data so it’s easy for biologists to use them. Otherwise it just becomes all these black boxes and they lose that empowerment. So the whole idea of our approach is to make tools to put in the hands of the biologists. We’re saying, “we want to teach you.” Nothing should be a black box. The way forward is to make more tools, have more visualisation, and make keeping in contact with the biological data easier to do.
What advice do you have for other researchers who are interested in joining the alliance?
Susan: I think having people come back and forth for visits is a good thing. Once people get to know each other, the internet makes it very easy. But only once you’ve established a common language, and that needs to be done in person. I think having a joint programme for postdocs will be great, as it’s the same idea – the human part is important.