Tom Baden | Michael D. Fox | Alan Gow | Michael Halassa | Chethan Pandarinath | Luisa Alexandra Meireles Pinto | Randall Jeffrey Platt | Mohammed Uddin | Jun Yao | Bao Zhaoshi
Meet the shortlist
Tom Baden, University of Sussex, UK
One of the things that most excites me about my field of research is that I love stumbling across “weird” results and gradually, through experiments, coming to understand what they mean. Most of our work is in some way the result of some prior stumble - it’s a very engaging way to work as you never know what comes next!
Just as open hardware development is almost never a one-person effort, I cannot name one individual person who has particularly inspired my work but the concept of open hardware itself inspires me profoundly. Movements are not born from the leader, but the early followers. Paraphrasing Derek Sivers from his famous TED-talk: A leader without followers is just a lone nut!
What drew me to my current research path was less a single inspiring moment and more a gradual process. I first started to get involved in the field of “Open Hardware” some five or six years ago. At that time, scientists and hobbyists were just starting to discover the utility of things like 3D printing or low-cost microcontrollers for their own projects. Browsing through online repositories that showcase other people’s designs you’d come across a prototype for a little lab-toy every now and then. For example, I came across a simple 3D printed pipette that used a balloon spanned between two plastic halves and a piston to generate a suction effect. The pipette was not very precise, but it was enough inspiration for me to have a go at improving it. When I posted my design online, I got a lot of feedback from others with ideas for further improvement. Some of these people took the challenge very seriously. Five years on, if you now go to google and type “3D printed pipette” you will find a vast diversity of designs, most of them much better than what I did at the time. I think it is the realisation that community-driven innovation really works which ultimately led me to invest more and more time in this field. Labs are full of expensive and over-engineered tools. If we find we can build a useful pipette, let’s try our hand at more complex machines.
This also synergises very nicely with my work within TReND in Africa (www.TReNDinAfrica.org) – a science education NGO that I co-founded in 2011. Part of our work on the African continent seeks to improve the research infrastructure on the ground, and here the possibility to build useful lab equipment for a fraction of the commercial cost, and using local resources, is of course very attractive.
Open hardware starts in the real world, and it is here to stay. If you build something, there is no reason that you cannot immediately use it. Beyond that, open sharing of good build instructions is critical. That way others can reproduce, adapt and improve designs. The self-propagating spread of these possibilities is very real already.
One day I believe that open source hardware will be as ubiquitous as open source software is today. Commercial hardware companies will then have to adjust their business strategy – perhaps shifting towards increasingly becoming service providers. For example, they may offer to procure parts, and/or assemble and test openly available designs for a fee. In fact, this is already beginning to happen. Of course, there will always be hardware that is simply too specialised or complex to be readily turned into an open hardware design. But a new balance will have to be found that favours an open model of product design for all but the most specialised tools.
I have the great fortune to work with a fantastically interdisciplinary team, both within the immediate lab and across our local community. In the lab itself we have field-biologists, physiologists, molecular biologists, physicists and engineers. This creates a powerful dynamic, where no project remains confined to a specific discipline. In fact, we have a little lab rule: Anyone “new” needs to build something. It doesn’t really matter what they build, perhaps a little tool they will need for experiments, or simply to recreate someone else’s design based on a paper. Once you have built something, it takes away the fear from building more things. This means that there is a lot of necessity-driven innovation for all those little hurdles that one inevitably comes across in the lab. We aim to translate those innovations into build instructions for interested colleagues, either as formal publications, or simply as deposits on our lab’s GitHub.
Michael D. Fox, Harvard Medical School, USA
During my second year of medical school, a patient with Parkinson’s disease was rolled into our classroom in a wheelchair. His right hand was shaking uncontrollably, and his stiffness was so severe that he was unable to stand. At that point, a doctor turned on electrodes that had been implanted in his brain. His tremor stopped. He then stood up from the wheelchair, walked across the room, and wrote his name on the chalkboard. I knew then what kind of doctor I wanted to be and what kind of treatments I wanted to work on.
Each day I have the opportunity to unlock mysteries of the human brain, use that knowledge to help patients, and mentor brilliant students in the process.
We have long suspected that brain circuits are a key to understanding and treating symptoms of brain disease. However, we lacked a wiring diagram of the human brain sufficient to identify these circuits. Thanks to advances in brain imaging and large international collaborations, we now have this wiring diagram. This neuroscience resource has been a game changer, allowing us to finally map symptoms to human brain circuits and identify therapeutic targets for brain stimulation.
Once we know which human brain circuit is responsible for a given symptom, we can target this circuit with techniques such as deep brain stimulation or transcranial magnetic stimulation to provide symptom relief. This approach has already led to success for symptoms of Parkinson’s disease and depression and might be applied to symptoms for which we currently have no effective therapies.
My ultimate goal is new treatments for brain disease and insight into the “big questions” such as consciousness and free will.
Alan Gow, Heriot-Watt University, UK
I’m working in an area that I think has, and will continue to have, and important role to play for people’s lives. As we’re living longer, many more people will likely experience some changes in their thinking skills, but that will vary from person to person. I’m keen to better understand those changes to try and develop ways that we might all maintain, or even improve, our thinking skills throughout midlife and into old age.
Over time, I’ve become more and more interested in building from identifying the factors that might protect our thinking skills, to developing and testing interventions based on those observational findings. I particularly focus on real-world activities, that is, things that might already exist within our communities in terms of adult education or engagement opportunities. The hope is that if we can better understand how those accessible activities might benefit our thinking skills, we’ll have a better chance of supporting people to do more of those things, rather than something that might be designed from scratch within a research centre but that might not translate well to people’s lives. Along the way though, I also want to better understand what people think about their thinking skills changing as they age. If we know the beliefs or fears that people have, we can hopefully more effectively communicate the ways in which lifestyles and behaviours might have been beneficial.
We know that as we age there are potential changes in our thinking skills. However, the variation from person to person directs our attention towards the opportunities for people to retain their thinking skills as we age. As maintaining our thinking skills is related to quality of life and independence, it is really important. Changes in thinking skills is also a concern people have as they age, worrying that these are inevitable or that these might be a sign of something more serious. While some people who show these declines do develop memory impairments or dementia, many do not, and so with this work we want to provide real-world, practical and accessible ways for people to maximise their brain health for as long as possible, in the same way we’ve seen changes in the ways people might consider their heart health.
I’d like to be able to contribute to our knowledge of the concrete actions people can take to better maintain their thinking skills. We can use that knowledge in directly speaking to people about those things, to raise awareness at the same time as balancing people’s concerns, while also working with our partners such as Age UK and Age Scotland to see where support is needed to ensure everyone has access to those kinds of beneficial activities. Ultimately, I’m interested in the kinds of activities and engagement opportunities that might benefit our thinking skills as we age, and by focusing on real-world activities I hope that we can provide clearer evidence for the aspects of mental, social or physical engagement that promote brain health so that activities and programmes might be better supported and available to everyone.
Michael Halassa, McGovern Institute for Brain Research, MIT, USA
Two things excite me about our research; people and discoveries. I am excited to show up to work and find ten other people in my lab who are equally driven about similar questions that lie at the edge of human knowledge. Their energy is infectious, and I am humbled that they have trusted me with a few years of their lives.
The discoveries we make also require a fair amount of detective work. The data we get from our measurements of behaviour or neural activity doesn’t immediately tell us what is going on, so we have to build models and iteratively refine them. That whole process is super-exciting.
One of my patients, who I’ll call Mr. R, and who had a diagnosis of schizophrenia was an early source of inspiration and motivation for me. He was a 19 year old kid when we started working together, and he was quite charming and engaging. Over the two years we worked together, he could eloquently describe the disorganized thinking that was becoming an increasing part of his reality. He could explain to me that, although he understood the unlikely nature of his beliefs (for example, that random strangers on the subway were out to hurt him), he was still unable to discard them. Having this glimpse into his internal logic continues to shape the types of questions I pursue around the circuit mechanisms of inference and decision making. Sadly, I lost touch with Mr. R; I often think of him and hope that my work will one day help him and others in his predicament.
The study I am working on now was spurred by a basic desire to understand how the brain gives rise to the mind. I also am driven to help those whose lives are disrupted by a disordered thought process, as observed in conditions such as schizophrenia. So I guess I am motivated by these two factors; basic philosophy (how does the brain give rise to the mind?) and helping some of the currently intractable psychiatric disorders that impact afflicted individuals, as well as their families.
Electrical stimulation of the thalamus, the part of the brain that my lab has focused on, has been shown to improve arousal and cognitive function in disorders of consciousness. This result has been replicated now with non-invasive ultrasound stimulation. My real hope is that by understanding the brain circuits that underlie the generation of complex thought, we will be able to do something about disorders such as schizophrenia using similar non-invasive neural stimulation methods. I think this would be an amazing application with a reasonable chance of success.
I hope that my work will ultimately change the course of illness in schizophrenia and at the same time I hope that I can foster successful scientific careers for those that I mentor.
On top of that, I aspire to build a machine that can reason as humans do, as this would require a satisfyingly high-level understanding of the mind, but could be beneficial for the quality of life for many.
Chethan Pandarinath, Emory University and Georgia Tech, USA
Neuroengineering holds tremendous potential for developing new methods to help treat brain injury and disease. In the past, the options we’ve had for treating brain disorders were either medication or surgery. There’s a growing recognition that biomedical engineering solutions, such as implanted devices, can play an important role here.
We already have a rich history of using electrical stimulation in the brain, including deep brain stimulation for Parkinson’s disease and other movement disorders, and cochlear implants to restore hearing for people who are deaf. We’re beginning to see these applications expand to closed-loop brain stimulation to epilepsy, depression, psychiatric disorders, and memory impairment.
I think there’s tremendous potential for devices that can understand the state of the brain and respond appropriately. We are developing technologies with a focus on brain-machine interfaces for people who are paralyzed from conditions like spinal cord injury or Amyotrophic Lateral Sclerosis. In these conditions, the connection between the brain and the body has been disrupted, either through injury or disease.
For example, when a healthy individual thinks about moving their arm or speaking a sentence, the brain sends signals down to the relevant muscles to drive the requested movement. When a paralyzed individual tries to move or speak, unfortunately those signals never make it from the brain to their muscles. However, they can still think about making the movement, and by implanting tiny electrical sensors in the brain, we can monitor electrical activity related to their movement intention, and use this information to do something useful for them.
For example, when they think about reaching and grasping a coffee cup, we can use electrical stimulation to drive their muscles in the right pattern to control their arms and hands and execute the movements they want. Or when they try to speak, we can translate the electrical activity we record into their intended speech, and generate this speech for them. What sounded like the stuff of science fiction 10 years ago is rapidly becoming achievable through breakthroughs in neural interfacing technology and our understanding of brain function, and we have the opportunity to harness these breakthroughs to really impact peoples’ lives.
Luisa Alexandra Meireles Pinto, Life and Health Sciences Research Institute – University of Minho, Portugal
What most excites me about my work, is the possibility to perform important fundamental research but also add translationally relevant knowledge to the field of neurosciences, where we are still in an embryonic stage of understanding, compared to other areas of health sciences research. In particular, and regarding the context of my current field of research, recognizing that psychiatric disorders have a biological, visible and measurable basis represented a major step for investigation in this field, as it signified the shift to a neuroscience-based approach of this medical condition. This has opened the possibility to act upon it in a tool-oriented manner but that inherently depends on the how well we understand the biological basis of these disorders.
What really interests me about my current research is the possibility of providing novel insights into the cross-talk between astroglia and the pathophysiology of depression implying new directions for clinical research and improved therapies.
My first important inspiration came from my PhD supervisor, Dr. Magdalena Götz. She is definitely an excellent teacher and mentor, highly motivated about her research and pushing herself hard to pursue her goals. I could never see her giving up in front of an obstacle! She is, in my perspective, a great female champion for Science, always fighting for research innovation with high impact for brain sciences and for society. She was always a true inspiration to me. Most importantly she taught me to never give up on my goals no matter how difficult and to pursue my research always aiming to bring novelty to the field, with the highest standards of excellence and ethics.
My PhD studies led to the discovery of the essential role of AP2y in glutamatergic neurogenesis and visual acuity. After that necessarily basic project, I sought a postdoc where I could test and see translational aspects of my findings by designing a project based on a genes-to-organism approach; I chose to focus on the modulation of adult hippocampal cytogenesis in the context of depression. Happily, that pathway led to an editorial commentary in The NEJM (J. Yager, 2013) in which my studies showing the potentially important role of astrogliogenesis in the pathophysiology of depression were highlighted. That appreciation spurred me to build a work plan, pursuing investigation of how glio-plastic mechanisms participate in the manifestation of depressive behavior.
Depression affects around 300 million people worldwide and is the leading cause of disability. Moreover, more that 30% of the depressed patients do not respond to any of the available therapies. As such, finding novel targets for disruption is of major relevance for the development of novel, more effective therapeutic approaches.
Glial cells have been mostly disregarded in the context of mental health, namely depression. This project will provide an innovative and integrated view on the importance of hippocampal astroglial plasticity and function for the healthy and “depressed” brain, using cutting-edge methodology. It has the potential to open an entirely new array of sex-differentiated therapeutic targets for depression, promoting the re-investment of the pharmaceutical industry in neuropsychiatry and ultimately the development of novel therapeutic interventions to treat depression.
In fact, one of the major breakthroughs of this proposal is the fact that we envision to translate the basic knowledge regarding the role of both pre-existing and newly-generated astrocytes to the clinical setting. We will do this by identifying common imaging patterns of neural network recruitment between our preclinical model and a cohort of depressed patients that is being already evaluated.
I would like to break barriers by tackling the specific functional relevance of newborn astrocytes in the healthy and depressed brain, gaining advantage through lead discovery in depression and promoting the re-investment by the industry in neuropsychiatry. I expect this research to have significant societal end economic impact for the management of the increasing burden of depression worldwide.
Randall Jeffrey Platt, ETH Zurich, Switzerland
To me, the most exciting aspect of my work is that I get to guide a team of scientists through the unknown while learning about fundamental properties of the brain and creating real-world value through molecular technology innovation. The unknown is mysterious where there is no map, no instructions, and no rule book – only uncertainty. Every day we learn something that no one in history has ever known before. Everything we discover gets us closer to both the ground truth and solutions for improving human health.
I delight in apparently insurmountable challenges and there is no bigger challenge, which will certainly persist for the length of my career and centuries to come, than unravelling the complexities of the human brain. In the context of the neurodevelopmental disorder autism in particular, it is glaringly obvious how little we know about the biological underpinnings of the disorder. The entirety of what we know is somewhere along the lines of: we are reasonably confident that the disorder is heritable and involves facets related to neural circuit formation during development and how those circuits function in later life. However, beyond that we are mostly stumbling in the dark. Outstanding questions with reasonable supporting evidence include: Is it the cerebellum, striatum, or cortex that is important? Is it an activity-dependent neuronal signalling problem or is it inhibitory-excitatory imbalance? Is it a problem of the reward system? Is it the microbiome? Are all of these facets just a part of a more complex mechanism? Because of these shockingly disparate assertions in the community my entry into the field as a graduate student was riddled with exasperation, and through this process it became clear to me that new tools that span cells, circuits, and development are desperately needed – providing me with an exciting career-long challenge.
The brain is complex and current methods make it challenging to gain an integrated understanding that spans circuits, signalling, and development. While single studies using current methods can clearly provide fundamental insights, they are often limited in scope and thus fail to provide a complete functional understanding. What the field needs is a systematic methodology that integrates insights across modalities, scales, and time. One way to achieve this is to encode biological information into DNA, which can be permanently stored and efficiently sequenced – turning biological problems into sequencing problems. My laboratory established ‘transcriptional recording’, a method that leverages CRISPR spacer acquisition of RNA to continuously record transcriptomes in living cells (Schmidt, Nature, 2018). The real-world applications of this include living diagnostics and a flight recorder for mechanistic studies of health and disease. Imagine being able to eat a tasty yogurt containing engineered cells that traverse your digestive system and once examined noninvasively in a laboratory reveal seemingly everything about your health (a 23andMe of gut health). Imagine being able to observe the lineage relationship between all cells in a developing organism as well as the expression profiles of all genes throughout that time. Once we can identify the when and the where of a problem, we can address how does this happen and how can we fix it. These are the opportunities and challenges that face science and society in the coming decades, and transcriptional recording provides a foundation for tackling them.
The ultimate achievement for me would be to i) discover the underlying biological substrate of autism spectrum disorder, thereby providing a basis for patient stratification, diagnostics and personalized therapy; and ii) develop a therapy that improves the quality of life for patients and their families. I do not believe that the current tools and paradigms we have today are sufficient to tackle this problem and therefore a central focus of my laboratory is to develop innovative technologies and concepts that are.
Mohammed Uddin, Mohammed Bin Rashid University of Medicine and Health Sciences, United Arab Emirates
A child with an undiagnosed or unexplained cause of illness or developmental disorder is very distressing to parents and of course also impacts on overall health outcomes. Identifying genetic causes that can explain a child’s condition is the most exciting part of my work. Early diagnosis enables early therapeutic intervention that is critical for children to improve their neurodevelopmental milestones (i.e. speech, behaviour, motor movement).
It was my own mother who first inspired me to become a scientist. Her dedication towards my pursuit of education and research is my major source of inspiration. My mother was the most dominating personality in my life and always influenced me towards science. She taught me how to become an independent thinker and be relentless, the most essential qualities in a scientist.
My research process is highly collaborative and involves neurodevelopmental cohort analyses from US, Canada, UK, Middle East and Bangladesh. My exposure to these international research communities helped me understand how genomics can have profound significance on the health of children who are impacted by neurodevelopmental disorders. The primary motivation for my next path of research is the establishment of a personalized precision medicine healthcare system where, based on genome profile and multidimensional clinical data, precision diagnostics and therapeutics options can be determined. Genome editing (CRISPR/Cas9) and artificial intelligence are power tools to make precision medicine based healthcare a reality for neurodevelopmental disorders.
Although genetic diagnosis has made significant progress in the field of autism and neurodevelopmental disorders, the progress on early therapeutic intervention is extremely slow. The application of genomics and artificial intelligence is extremely important to fast track the detection of molecular interactions and targets for early therapeutic intervention.
The first real world application we might see from my work would be the use of the AI component to identify the causal variants and their downstream molecular interactions that bear unique signatures of neurodevelopmental disorders. This application can, I believe, be easily integrated into drug design. Secondly, the AI component can be extended to incorporate into multidimensional clinical data (i.e. MRI, EEG, IQ, or other psychological assessments) to map out genetic interactions with important phenotypic variables. I think the future of neurodevelopmental disorders clinical applications will be heavily dependent of genomics and AI driven platforms.
The genetic contribution for neurodevelopmental disorders is strikingly high. I would like to establish personalized precision medicine based health care for neurodevelopmental disorders that will apply genomics and artificial intelligence techniques to precisely diagnose conditions and tailor therapeutic options – a fully integrated platform that will assist future healthcare systems to make clinical decision based on a child’s genotypic and deep phenotypic profile.
Jun Yao, Tsinghua University, China
I made a research plan several years ago aimed at making clear the pathogenic mechanisms of bipolar disorder. Every time we succeed in taking one small step forward according to the plan or achieve some unexpected results to amend our model, I feel as though we are coming closer to the ultimate answer to treat the disease. This is what most excites me about our work.
I think what spurred me to the research path we are exploring now is the eagerness that people often show me - they hope I can give them an answer or a cure for the psychiatric disorder affecting them or their family members when they learn that I am a neuroscientist studying mental disorders. They believe that a researcher like me can understand what has happened to their family and what they can do to escape the disease. I gave a popular science lecture earlier this year. After my speech, the audience immediately surrounded me, very enthusiastically asking me lots of questions about different types of psychiatric disorders. Although many were not related to my lecture, I could feel that they viewed me as their hope. This type of feeling has given me a strong sense of calling and spurs me onwards.
Current animal models based on clinically identified susceptible genes have often failed to show spontaneous mood cycling, the core symptom of BD. However, intergenerational research has revealed that BD has a very strong heritability and the rate can be as high as 80%. This indicates that a fundamental cell deficit, probably at the molecular level, can be stably inherited within a family and result in BD symptoms. In my lab, we have been trying to combine the pluripotent stem cell and mouse models to find shared molecular deficits among subgroups of patients. We think this molecular pathway might contain some potential targets for drug development. I hope that our work can push forward the development and application of new drugs and therapies for the treatment of BD patients worldwide.
At a minimum I believe we will understand the overall picture for the neurobiological basis of BD. If we can find a way to conveniently and safely treat the symptoms for most patients, to reduce the impact of the disease to little more than a fleabite, we will have accomplished something very worthwhile.
Bao Zhaoshi, Beijing Tiantan Hospital, Capital Medical University, China
Day to day, the most exciting moments in my work include when an unconscious patient wakes, a “thank you” from a patient after surgery and a smile after recovery. When I was an intern, I carried out a lumbar puncture on one particular post-surgical patient almost every day. A lumbar puncture is an invasive and very unpleasant procedure. However, this patient never complained about the pain and smiled through the procedure. I couldn’t help asking him why. He said that the operation was minor and didn’t cause him pain. I know that what he said was impossible but he trusted me and believed that, as a neurosurgeon, I could cure him, His belief was a great encouragement to me. I think the patients’ trust in me to solve their problems is what excites me most about my work.
The supervisor of my Master’s and Doctoral studies, professor Tao Jiang also inspires me a great deal. He is vice director of Beijing Neurosurgical Institute and Director of Glioma Center, Department of Neurosurgery, Beijing Tiantan Hospital. When I first studied under him a decade ago, there were few doctors focusing on glioma research in China. Professor Jiang taught me to keep moving forward and never give up. He said: “the scalpel is only one of the weapons of a neurosurgeon against brain disease, research is the other”.
Glioma is the most common and aggressive brain cancer in adults. According to the WHO classification of tumors of the central nervous system, gliomas are categorized into lower grade gliomas (LGGs) and glioblastomas (GBMs). Distinct from primary GBM that usually develops de novo in elderly people, secondary GBM (sGBM) carrying the IDH-mutant, typically progresses from LGG within five to 10 years from diagnosis. I want to evaluate efficacy of compound PLB-1001 in a further phase 2 clinical trial for recurrent glioma patients with ZM fusion and reveal the genomic landscape of glioma recurrence and progression, elucidate mechanisms of glioma recurrence and patterns of glioma evolution and establish adrug screening system targeting glioma recurrence-associated pathways.
In the next phase of my research we will establish a drug screening system targeting glioma recurrence-associated pathways identified from this project. Using this drug screening system, recurrent glioma patients will benefit from drugs sensitive to glioma recurrence and a better survival time after tumor relapse. Patients with ZM fusion will be benefited from PLB-1001 for better overall survival.
Ultimately, I’d like to see patients be treated with precision therapy using the drug screening system. When a patient is diagnosed with glioma or when it recurs, we will know to which drugs the tumor is sensitive.
I know I cannot cure every glioma patient. Only some patients can be benefited from my research. But curing glioma seems like a Noah’s Ark to me. Only some people can board on the ark. I want to do more research and do my best to give boarding tickets to more patients who want to board the ark.
Note from Nature Research:
Nature Research carried out extensive promotion of the Driving Global Impact Awards all over the world and was surprised by the limited diversity of the entrants, particularly in terms of gender. A little preliminary investigation revealed that low numbers of female entrants is a problem common to awards in the STEM fields globally. Between 30% and 40% of principal investigators are female, with some variation between disciplines; typically, fewer than 10% of entrants in STEM awards open to all genders are female.
Nature Research has therefore decided to collaborate with a number of other organisations in STEM-related fields, leading a research initiative to find out why this is and how it can be addressed.