Collaboration — a key part of scientific discovery

The parable about the blind men and the elephant has much to teach us about collaboration. In the story, a group of men feel different parts of an elephant – but only one part. One man proclaims he feels a wall. A second man states he feels a tree. A third, a fan. The others feel a spear, a snake, a rope. Pieced together, the men realize the parts are the elephant’s body, legs, ears, tusks, trunk, and tail.

At its core, the parable is about relative experience when facing the unknown. Scientists, too, can approach a similar challenge from different yet complementary perspectives.

In an increasingly interconnected and complex world, collaboration is more important than ever for progress in science. By coming together, scientists can share knowledge and ideas to solve complex problems, learn new skills, and advance their careers. Researchers at Whitehead Institute recognize the importance of collaboration when taking on big challenges in science. Below are just some of the ways in which they have reaped the benefits of collaboration.

Bringing expertise to multidisciplinary research questions

Some challenges in science require pooling knowledge and resources from different places. By working together, scientists can develop powerful approaches and findings that might not have been possible for a single lab to have achieved.

For Whitehead Institute Member Iain Cheeseman’s lab and Broad Institute of MIT and Harvard Core Member Paul Blainey’s lab, this has meant combining experimental and computational approaches. The two labs developed an approach for removing the function of particular genes across hundreds of cells at a time, and then visualizing the effects under the microscope. The results were compiled onto a web portal called Vesuvius, which anyone can access.

The relationship between the Cheeseman and Blainey labs started off informally. “It’s more like we exchanged reagents and ideas, and our project became more concrete over time,” said Kuan-Chung Su, a postdoc in the Cheeseman lab and co-first author of the corresponding study.

For this project, both labs shared tools to generate data for this platform. Cheeseman’s lab contributed components of the CRISPR/Cas9 gene editing system that they used to turn off certain genes in a sample of  cells. Blainey’s lab developed the technology used for measuring gene expression in the cells.In order to identify differences in gene function, cells are grouped by phenotype – or physical characteristic – in image-based screens.

Together, the labs met to make sense of the data. The researchers were astounded by how much information they could pull from it. “We gained insights on cell processes beyond cell division and the cell cycle, which is our lab’s main focus,” Su said. “We thought this data would be useful to other scientists, and we wanted to share it.” From there, the Vesuvius portal was born.

Generating new ideas

Scientists from diverse disciplines sharing ideas can lead to approaching problems in ways that have not been explored. Alessandra Dall’Agnese, a postdoc in Whitehead Institute Member Richard Young’s lab, is particularly interested in condensates, or small membraneless droplets within cells that play an important role in many aspects of gene regulation.

Dall’Agnese collaborates with scientists from Massachusetts Institute of Technology (MIT), as well as clinicians from Massachusetts General Hospital and Dana-Farber Cancer Institute, in order to understand how condensates play a role in gene expression.

Clinicians offer their unique perspectives from working directly with patients. “Having a conversation with a physician can guide you to important problems that a scientific paper may not illuminate,” Dall’Agnese said.

About once per month, Dall’Agnese and her colleagues meet to discuss their projects and help each other move them forward. She recalled a time when she was having difficulty figuring out how a change in a particular protein within a condensate would have an effect on cellular signaling. Arup Chakraborty; Institute Professor of Chemical Engineering, Physics, and Chemistry at MIT; offered a way of seeing a solution that made sense from a physics standpoint.

“Since then,” Dall’Agnese said, “I’ve been able to answer questions at conferences with answers that may feel more intuitive for a greater audience.” The sometimes unexpected synergy between different fields can sometimes provide for a more holistic approach with which to tackle tough questions in science and medicine.

“Science is very competitive,” Dall’Agnese said. “The more we can help each other succeed, the more at ease we will be. We are all addressing different questions with similar concepts, but they build upon each other. There is a constructive and empowering atmosphere between us.”

Mentorship opportunities

Collaborative research can also provide scientists with mentorship opportunities. Chen Weng, a postdoc at Whitehead Institute, is part of a co-mentorship with Whitehead Institute Member Jonathan Weissman and Vijay Sankaran, a physician scientist at Boston Children’s Hospital, associate professor of pediatrics at Harvard Medical School, and former postdoctoral fellow at the Whitehead Institute. Together, they research the behavior of stem cells that give rise to blood cells, as well as how these cells change as we age.

Different types of blood cells are made from hematopoietic stem cells, or HSCs, by a process called hematopoiesis. More than thirty percent of people over seventy years old have clonal hematopoiesis, meaning that one of the HSCs expands and crowds out the other ones. This condition carries with it a tenfold higher risk of developing leukemia. Weng wants to know how the behavior of HSCs differs between young and elderly people.

Weng joined the labs of Weissman and Sankaran in 2021. He initially reached out to Sankaran. “We were thinking about this cool idea about understanding blood and aging,” Weng said. “But, we realized the existing technology to do this from human samples was not powerful enough. We wanted to do something even better.”

That is when the two reached out to Weissman. He and his colleagues; including postdoc Dian Yang, former graduate student Matthew Jones, Tyler Jacks at the Koch Institute for Integrative Cancer Research, and Nir Yosef at the University of California, Berkeley and the Weizmann Institute of Science; developed a way to engineer cells to trace the evolution of a tumor over time. Building on earlier work from Sankaran and biologist Aviv Regev, while she was an investigator at the Broad Institute, they sought to adapt the same powerful technology Weissman uses in mice and develop new technologies to enable research in human cells.

“Developing a system to use with patients could provide basic biological insights and have a strong clinical impact, and I think that’s where the synergy comes from,” Weng said. “More important than the experiment itself, though, are the thoughts and views behind it. We have a lot of conversations about seeing what we can push forward for better understanding of human health.”

Weng spends roughly half of his time at Weissman’s lab, and the other half at Sankaran’s lab. About once a month, the three of them meet to discuss the collaboration. Weissman provides expertise on developing techniques used to study genetic material in cells, while Sankaran gives expertise on hematology and blood cell production Together, they provide Chen with key guidance across these diverse fields, all the while innovating and addressing important biological questions.

“Collaboration in science is essential these days because the knowledge base is so huge now,” Weng said. “No individual person will be an expert in every field in biology. Without collaboration, I feel many things would be much harder to accomplish. We have a lot to learn from each other.”