4 Years In: A Look Back and a Look Forward for the Neurodegeneration Challenge Network

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In 2018, we launched the Neurodegeneration Challenge Network (NDCN) with the vision that by attracting new talent, ideas, and perspectives to the field, this network of collaborative interdisciplinary scientists would both challenge and advance our understanding of the biology underlying neurodegenerative diseases. Scientifically, we aspired to motivate the collective field to shift the approach to neurodegenerative diseases to a framework, where these diseases — currently addressed largely as distinct diseases and problems — are considered more holistically as a class of disorders with common features, mechanisms, and solutions.

Four years in, we’re reflecting on the Network’s successes and learnings, and sharing our vision for the future. We’re also excited to announce new funding cycles of the Ben Barres Early Career Acceleration Award and the Collaborative Pairs Award.

Below, read more about what we’ve learned from NDCN in our first four years, and where the Network is headed next.

What We’ve Learned

In the past few years, the NDCN has made a lot of progress: we’ve launched several RFAs ranging from early career support for fundamental neuroscience research to collaborative grants that bring together interdisciplinary pairs of scientists to explore bold, innovative ideas that will help us better understand neurodegeneration. We’ve also seen the value of supporting the development of high-quality research tools and computational approaches that benefit the broader research community.

We have learned a tremendous amount from our grantees in terms of exciting scientific discoveries and the ways that programmatic support can amplify and broaden the impact of funding. Some of our key lessons:

  • The Challenge Network itself is a tool and forum to deepen the scientific contributions of our grantees, creating new opportunities for collaboration and impact beyond the initial funded proposal.
  • It’s essential to invest in early career researchers as the next generation of leaders and innovators in a field.
  • Fundamental biology is a lens to understand and address disease, and disease can be a lens to better understand fundamental biology.

Networks Spur New, Innovative Interdisciplinary Collaborations that Advance Research

Our vision for the Neurodegeneration Challenge Network has been to build a collaborative research environment that goes beyond the typical consortia and is more than the sum of its parts. We have explicitly cast a wide net aimed at breaking down disease and methodological siloes that existed in the field. We brought together world-class scientists, technology developers, and clinicians, with diverse and wide-ranging expertise and empowered them to think creatively and tackle hard problems. This network approach has enabled scientists to collaborate in new and exciting ways to further research around neurodegeneration and fundamental neuroscience. Importantly, many of our grantees have told us that being a part of this Network has been as impactful for their work and careers as the funding.

Since its launch in 2018, NDCN has grown into a vibrant community of more than 120 principal investigators and their labs, including over 500 students, postdocs, and research scientists. Researchers come together frequently through webinars, working groups, training programs, and annual investigator meetings. These touch points have spurred numerous collaborations, often in unpredictable and exciting ways.

Researchers within the Network come together to share data and tools, discuss ideas, troubleshoot challenges in their work, and co-develop new research approaches. This collaborative model benefits not just NDCN investigators, but also the wider research community. A great example of this is the NDCN iPSC working group which, in partnership with the NIH INDI project and Jackson Labs, has led to the generation of a publicly available collection of well-validated, neurodegeneration-associated iPSC lines that are an open resource for researchers everywhere.

In seeing the kinds of exciting scientific partnerships that can emerge organically by bringing talented and engaged researchers together, we’ve since launched a number of new grant mechanisms specifically intended to spark collaboration within the Network. The first cycle of Collaborative Pairs Pilot Projects kicked off in 2020 with a focus on cellular mechanisms of neurodegenerative disease. In 2022, inspired by some of the work we saw developing within the NDCN on rare neurodegenerative diseases and with patients as partners, we launched Patient-Partnered Collaborations for Rare Neurodegenerative Disease, a program that brings together research teams and patient advocacy groups to tackle fundamental questions at the heart of rare neurodegenerative disease.

Human iPSC-derived astrocytes and neurons. Photo courtesy of Parker Grosjean, Kampmann Lab.

Investing in Early Career Stage Scientists is Critical

Early career scientists are the future of fundamental neuroscience and neurodegenerative research. They come from a wide range of scientific backgrounds and institutions and bring unmatched creativity to the table. The inaugural and flagship grant program for NDCN was the Ben Barres Early Career Acceleration (ECA)Award, a five-year investigator award that supports talented early career scientists who are new to the neurodegeneration field. The Ben Barres ECA award gives scientists the runway and freedom to pursue science creatively and unbounded by specific deliverables and milestones in a way that would be typical for project-based grant awards. As a mentored award, ECA grantees new to the field benefited from both mentorship from senior investigators and peer connections in the Network, allowing them to supercharge their work, develop new connections and collaborations, and pursue new lines of inquiry.

An innovative feature of the NDCN compared to many other neurodegenerative disease grant programs and consortia is the breadth of scope and strategy. A goal of the NDCN is to break down research siloes, reconceptualizing how we approach neurodegenerative disease. The initial Ben Barres Early Career Acceleration cohort is a great example of this: the 17 ECA investigators pursued a wide range of questions, from immunological influences, gut-brain mechanisms, stem cell and organoid-based approaches for modeling cellular mechanisms of disease, computational approaches for disease classification, and new models for cellular interactions as drivers of disease. The work of this cohort has been united by their bold vision and cutting-edge approach to science.

Pyramidal neurons imaged with confocal microscopy. Photo courtesy of Henner Koch.

Fundamental Biology Is Lens to Understand and Address Disease

The NDCN was launched with a focus on fundamental biology and the view that while there are a number of funders and philanthropies focused on translational and clinically-driven approaches to tackling neurodegenerative disease, there are still relatively few programs that are centered on basic biology and, in particular, that are open to researchers with more limited disease-relevant experience. The first phase of the NDCN had a focus on the molecular and cellular mechanisms underlying neurodegenerative disease. Genetics has given us a window into the genes and pathways that go wrong in disease, but offers only a limited picture of what’s actually going wrong at the cellular level, let alone how these cellular deficits play out at the level of circuits and systems or in the whole body, across the span of life.

As we embark on the next phase of the NDCN, we are also expanding the scope of the Network. With the view that a general understanding of cellular and circuit mechanisms of healthy brain function will be a critical foundation for understanding and ultimately solving neurodegenerative disease, the next phase of the NDCN will expand to cover a broader range of fundamental neuroscience. We have seen tremendous impact and innovation come from bringing together researchers, clinicians, and patients whose work is centered on disease-relevant questions with researchers and technology developers whose expertise and background are in other areas of research. And we also recognize the critical role that basic research has had in laying a foundation for understanding and ultimately treating disease, often in unpredictable ways. For instance, CRISPR technologies now enable us to edit the human genome, and RNA vaccines have played a key role in managing the COVID-19 pandemic.

Neuronal image. Photo courtesy of Samuel Powell.

What’s Next

With all we’ve achieved and learned in the first four years of the NDCN, we’re eager to see what the next five years will bring. We are excited to bring innovative, bold ideas and new talent into the Network through new cycles of the Ben Barres Early Career Acceleration Award and the Collaborative Pairs Award. These funding opportunities are open to the global science community, and we look forward to expanding the geographic representation of the NDCN.

The Ben Barres Early Career Acceleration award supports early career academic investigators, especially those who are new to the field of neurodegeneration. We’re interested in science that brings new approaches and technologies to the study of neurodegenerative disease and fundamental neuroscience. Applications are currently open through April 20, 2023. Learn more and apply now.

With the view that a better understanding of the fundamental mechanisms of brain function during healthy aging will also be critical for contextualizing the types of processes that go awry in neurodegenerative disease, for this new cycle of the Collaborative Pairs program, we are excited to be broadening the scope of our network to also support investigations into areas of fundamental neuroscience where we see potential to complement or synergize with our existing network. These areas include basic investigations into the cellular, molecular, and circuit mechanisms of memory and cognition and sleep that impact nervous system function.

The Collaborative Pairs Pilot Project Awards is an opportunity for pairs of investigators who have never been funded to work together to explore innovative, bold, out-of-the-box ideas. Pairings should take an interdisciplinary approach to address knowledge gaps in our understanding of the fundamental neuroscience driving neurodegeneration, sleep and memory and cognition, in ways that leverage each researcher’s unique, complementary area of expertise. For example, we’re looking for collaborative research projects that bring together experimentalists with computational biologists or technology developers, or collaborations that bridge multiple disciplines like immunology, cell biology, neurophysiology, genetics, biochemistry, stem cell biology, and bioengineering.

Each pair is required to include at least one early- or mid-career researcher. Collaborative Pairs teams that receive pilot project funding and have successfully progressed their project will be eligible to apply for four years of extended research support. Read more about the 30 collaborative pairs supported under cycle 1 of the Collaborative Pairs program. Applications for the Collaborative Pairs Pilot Project Awards will be open from May 9 to June 22, 2023. Learn more.

We’re excited by the scientific advances achieved through this collaborative, interdisciplinary network, and with the expanded scope of the network, look forward to the scientific discoveries that will emerge over the next five years.

Learn more about the Neurodegeneration Challenge Network and sign up for our mailing list to hear about future funding opportunities.

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Chan Zuckerberg Initiative Science

Supporting the science and technology that will make it possible to cure, prevent, or manage all diseases by the end of the century.