What type of science would you be using if you were trying to find a cure for cancer
Analogy past Oli Winward
When Daniel Stover was doing his postdoctoral research in a jail cell-biology lab at Harvard Medical School in Boston, Massachusetts, he ran into a trouble. He was studying a type of breast cancer, trying to piece of work out whether genetic differences between one part of a neoplasm and another contributed to the cancer's resistance to chemotherapy. He had plenty to work with — genetic information from hundreds of tumour samples — but no thought how to handle it all.
"I had generated an immense corporeality of sequencing data and couldn't discover everyone to analyse it," says Stover, now an oncologist at the Ohio State University's Comprehensive Cancer Center in Columbus. And then, with the help of a bioinformatician in the same lab, he started studying computational biological science, which became the focus of his studies. "I establish that I loved working with data," he says. All the papers he published as a postdoc ended upwardly being based on informatics, and now his own lab, which he set upwardly last September, focuses on clinical computational oncology.
Stover'due south lab aims to fill the infinite betwixt the calculator experts who develop data-handling algorithms and the clinicians who focus on patient intendance, treatment and clinical trials. "In between, there'due south a gap, and nosotros try to fill up that void and take these astonishing algorithms and apply them in clinical settings," he says.
Stover says the collaboration changed the direction of his career, in part because it gave him new skills that he could employ in working with other researchers.
Cancer research has become highly multidisciplinary. The field now includes not just clinicians and molecular biologists, merely also computational biologists, statisticians, nanotechnology experts and chemical engineers. And that creates challenges for all those researchers. How practice they work with people who have different areas of expertise, each with its own basic assumptions and specialized language?
Nancy Krunic, who works for Novartis Pharmaceuticals in Cambridge, Massachusetts, heads the company's Future Precision Medicine Diagnostics group, which is developing assays, software and other engineering science to aid in diagnosis. "No one person or one department, or one lab, is going to take all the tools they need to tackle the problem," she says. "You absolutely need diverse backgrounds and subject-thing expertise."
Whether they're big pharmaceutical organizations or medical-device companies (Krunic previously worked at Luminex Molecular Diagnostics in Toronto, Canada), industry groups targeting cancer must form multidisciplinary teams, Krunic says, if they are to define and tackle bug in ways that are scientifically, clinically and commercially feasible. Too as scientists and technologists, these teams will include people with expertise in, for case, marketing and regulatory issues, says Krunic.
Beyond biology
Programmes exist to promote cross-fertilization between disciplines. The U.s.a. National Cancer Found (NCI), for instance, established a Physical Sciences in Oncology initiative in 2009 to squad cancer biologists with physicists, mathematicians, chemists and engineers. Those disciplines come at cancer in a diverseness of ways. Chemical engineers devise new diagnostics and develop nanoparticles to conduct drugs to tumours, or to act as dissimilarity agents that make smaller tumours visible in imaging. Physicists and bioengineers study the effect of mechanical forces on tumour growth and behaviour, and mathematicians develop computational models to explain the complex interplay between unlike cancer cells, blood vessels, healthy tissue and drugs.
For example, researchers are working to sympathise the physical effects of a tumour's environment. How does an increase in tumour stiffness bear upon the shape and behaviour of the cells within it? And when a metastasizing cell deforms to squeeze through tight spaces, what does the increased force per unit area do to the jail cell'due south nucleus — does information technology, for example, trigger processes that damage Dna? "It'south non just the physical forces, but that'due south an important aspect of what's being studied," says Nastaran Zahir, director of the Concrete Sciences in Oncology programme. Other projects include applying mathematical approaches such equally game theory to determine dosing strategies that will minimize the evolution of drug resistance, instead of applying the standard 'maximum tolerated dose' approach.
Zahir has feel of crossing disciplines. She earned her available's degree in nuclear engineering, and studied plasma physics before moving into radiations biology and getting her PhD in bioengineering in a cancer inquiry lab. And so she's aware of the difficulties. "Biological science has its own civilisation. Physics has a unlike culture," she says. "In physics, what you search for is sort of the ultimate truth — is there a law? But biology's very messy, and you don't necessarily accept an exact process." Considering biological processes modify in response to new stresses, it'south difficult to come up up with laws for how a targeted prison cell would react to a cancer drug, for instance.
Language barriers
To assistance span such gaps between disciplines, the NCI created the Scientific discipline of Team Science programme. Kara Hall, a behavioural scientist who directs the initiative, says it'south of import for people to share knowledge with those from other disciplines in a comprehensible mode. "That entails reducing the jargon that's being used, or finding means to define that jargon as you get along," she says. It is frequently helpful to use analogies to explain primal concepts in a field. Information technology's also useful for researchers to engage in 'team learning', in which individuals are tasked with gaining in-depth information on a topic and bringing it back to their colleagues. Hall says teams should reflect on how well they function, by discussing, for instance, whether their meetings are sufficiently frequent and informative.
Hall says that people must be open up when they approach specialists in other fields. It'due south important, she advises, to practise 'disciplinary humility' — to realize that all disciplines take both strengths and weaknesses, and to exist willing to acquire from fields other than your own. Finding a safe common ground to ask questions tin exist hard. "If I'm a psychologist collaborating with a geneticist, I may be afraid to ask a 'genetics 101' question because I might be seen as intellectually inferior," Hall says.
Other challenges in team science include the need for extra planning and direction fourth dimension, compared with individualized inquiry. The approach can also require more team meetings and more travel, when collaborators are located beyond campus or at other institutions. And some institutional structures have not all the same caught upwardly with the concept, Hall says. Promotion and tenure committees tend to expect mainly at the first and last authors of papers, she says. And that ways they might non recognize how much a middle author has contributed — even though, in teams, centre authors play a crucial part in the research. Yet, Hall says, her programme's surveys plant that trainees who had worked in multidisciplinary teams reported that their experiences had made them more than competitive in the job market.
Defining the goals of a project, planning its implementation and working out in accelerate how to resolve conflict are all of import parts of setting up a collaboration. The NCI offers the Squad Science Toolkit, an online resource whereby researchers tin can share data and mail news almost funding opportunities and job openings. Information technology as well helps to plan and support an annual Science of Team Scientific discipline conference, which focuses on ways to make team-based research more effective. The next meeting runs from 21 to 24 May at the Academy of Texas Medical Branch in Galveston. And the US National Institutes of Wellness offers what information technology calls a "prenuptial understanding" to help scientists prepare for problems that tin arise during a collaboration (see 'Making it work').
One early-career researcher taking a multidisciplinary approach is Viktor Adalsteinsson, who leads the blood-biopsy squad in the cancer programme at the Broad Constitute of MIT and Harvard in Cambridge. Although he earned his doctorate in chemical applied science, in 2015, Adalsteinsson knew from a young historic period that he wanted to help cure cancer. He did his PhD piece of work at the Koch Institute for Integrative Cancer Research, which was set up up at the Massachusetts Institute of Technology to bring biologists and engineers together under i roof. He helped to develop a system to isolate and sequence circulating tumour cells from claret samples, using his chemical-engineering education to deal with issues such as fluid dynamics and the corporeality of shear stress that cells could handle. At present in his own lab, he's trying to capture cell-free cancer DNA from blood to perform sequencing for precision medicine, reducing the need for invasive biopsies.
Ane of the ways in which Adalsteinsson and the people he works with stay upward to engagement is through frequent meetings and seminars, at which diverse specialists talk most their work. Having a network of colleagues who can explain research from other disciplines, or tell him whether a journal article is significant, is helpful, he says. "It's impossible to be an expert in every possible area, and knowing when to turn to others is really important."
Puddle expertise
Sometimes the trick lies in knowing what not to read. "Existence able to scan and reject a bunch of stuff is really important," says Heather Parsons, a medical oncologist and medico at the Dana–Farber Cancer Institute in Boston, who specializes in breast cancer and its biomarkers. She, likewise, emphasizes the importance of having a network of experts, adult through university and piece of work, with whom you tin can discuss questions.
Parsons collaborates with Stover and Adalsteinsson on the liquid-biopsy work. "I similar very much being role of this kind of a team," she says, "but information technology requires that you lot don't have an enormous ego and you lot don't listen asking about things you don't sympathise."
At Stanford Academy School of Medicine in California, Guillem Pratx gets members of his physical oncology lab to accept part in a journal lodge. They meet for an hour or and so to focus on a particular newspaper, allowing people from different disciplines to gain a proficient understanding of its importance. He besides requires them to nourish meetings exterior their field to broaden their knowledge. With plenty exposure, he says, scientists tin can become comfortable with the terminology and concepts used in other areas. "I detect the more I sit in these talks, the more I understand," Pratx says. "It's like learning a new language."
Pratx did his undergraduate and graduate studies in electrical engineering, and during his PhD studies he worked in a radiology lab, using graphics techniques from calculator games to improve the processing of medical images. He did his postdoctoral enquiry in radiations oncology, and he feels that using postdoc fourth dimension to larn about an surface area outside 1'southward core speciality tin pay off. It tin can be hard to be hired past a lab that specializes in a field far removed from yours, he acknowledges. But if there's some overlap, information technology tin can add valuable expertise.
Pratx'southward lab, which includes scientists with backgrounds in physics, engineering, chemical science and biological science, develops instruments, probes and algorithms for cancer imaging. The team is studying how the luminescence generated when therapeutic radiation hits tissue can be used to advisedly aim the otherwise-invisible beam. Ane challenge for such multidisciplinary teams is communicating to unlike members how they can tackle a problem, he says. Biologists often struggle to empathize what questions mathematical models tin can ask apropos the large data sets generated in cancer research — sets that include non but genomic and proteomic sequences, but besides imaging results and environmental information from medical records. It'due south of import that there's someone in the group who understands which statistical methods are best practical to particular types of data, and what the results do and don't show, says Pratx.
On the flip side, he thinks that engineers can focus too much on trying to come up with innovative techniques, and are sometimes less interested in applying what others have already developed. It's not enough for insights gleaned from information to be new, he says. They besides accept to be biologically relevant.
One trouble that Pratx sees is the one Stover experienced. Although the growth in data is increasing the need for computational specialists in cancer research, the competition from other fields for people with those skills is strong.
Matchmakers
Early-career researchers interested in forming collaborations need to network with people from other fields, and i obvious way is to attend conferences in those fields. But Jennifer Podesta, a molecular biologist and a specialist in the use of nanotechnology for drug commitment, says that merely attention a conference isn't enough. "Do a little bit of homework, and go in very much with an calendar of 'who it is I want to meet and what practice I want to leave of it?'" she says. "It's remarkable how many people recall they can show up, scrunch over and stand in the corner, and come abroad from it complaining that they didn't meet a collaborator."
Podesta, who runs the Cancer Research United kingdom Centre at Imperial College London, recommends working out the type of scientist you need for the project you have in listen, and so approaching department heads in your own university to see who they think might fit. Funding managers also tend to have a wide knowledge of which researchers take what expertise, and are usually happy to play matchmaker.
Getting funding for cross-disciplinary projects can exist challenging, especially for someone who hasn't nevertheless established a reputation, so Podesta suggests looking for small sums of coin internally, to fund a pilot projection with a new collaborator. Such projects demonstrate that members of the team can work together and produce viable ideas, making them more than attractive to funding agencies. The NCI's Physical Sciences in Oncology programme provides funding specifically for pilot projects.
Trying to proceed up with a field as dynamic every bit cancer inquiry is daunting. "We have so much information within our accomplish, and new discoveries are being fabricated every day," Adalsteinsson says. The primal to tackling all that data, Pratx says, is to overcome the tendency of many scientists to think they need to learn everything themselves. "I think it'due south an important skill when you're able to say, 'Perhaps I don't need to be an proficient in computer modelling. I can maybe piece of work with somebody else,'" he says.
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Source: https://www.nature.com/articles/d41586-018-04164-7
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