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Working together at the interface of physics and biology
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2014 Phys. Biol. 11 053010 (http://iopscience.iop.org/1478-3975/11/5/053010) View the table of contents for this issue, or go to the journal homepage for more Download details: IP Address: 130.133.8.114 This content was downloaded on 05/05/2017 at 08:25 Please note that terms and conditions apply.
You may also be interested in: Research at the interface of physics and biology: bridging the two fields Kamal Shukla A model for signal transduction during quorum sensing in Vibrio harveyi Suman K Banik, Andrew T Fenley and Rahul V Kulkarni Stochastic switching in biology: from genotype to phenotype Paul C Bressloff Statistical mechanics of tuned cell signalling: sensitive collective response by synthetic biological circuits M Voliotis and T B Liverpool Ask not what physics can do for biology—ask what biology can do for physics Hans Frauenfelder Transforming transportation David Smith
Physical Biology Phys. Biol. 11 (2014) 053010 (4pp)
doi:10.1088/1478-3975/11/5/053010
Perspective
Working together at the interface of physics and biology 1,2
Bonnie L Bassler and 2,3 Ned S Wingreen 1 Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544, USA 2 Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA 3 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA E-mail: [email protected]
1478-3975/14/053010+04$33.00
Abstract
Good communication, whether it is between quorum-sensing bacteria or the different scientists studying those critters, is the key to a successful interdisciplinary collaboration, Bonnie Bassler and Ned Wingreen provide a personal perspective on working at the interface between the physical and biological sciences. Keywords: interdisciplinary, physics, biology
Ned: My long-term collaboration with Bonnie began fortuitously when we met in the Mexico City airport baggage claim in 1999. We were both going to the BLAST (Bacterial Locomotion and Signal Transduction) Conference. My background is in theoretical condensed matter physics, and at that time my growing interest in biology was not accompanied by much actual knowledge. I recognized Bonnie as a Princeton University biologist, and since I was living in Princeton and working nearby at the NEC Research Institute, I summoned up my courage and introduced myself as a physicist trying to move into biology. Bonnie: Ned and I chatted as we walked to the bus that was taking participants to the conference. I, trying to be friendly, asked about his interest in the physics of two-component signaling systems (bacterial two-component proteins are the singular focus of the meeting). Ned said ‘What’s a two-component protein?’ I said (agog) ‘You better sit by me on the bus or you are going to have the worst week of your life’. We had an enjoyable two-hour tutorial on the way to the conference site, with many other biologists piping in over my shoulder to describe to Ned the basics in the field of bacterial signaling. Ned: What a great introduction to biology, and what an inspiration to learn more! By the end of the meeting, I felt I owed Bonnie some deep ‘physicist’s’ insight into bacterial quorum sensing. In an effort to fulfill this obligation, over the next two years, I regularly presented ideas to Bonnie, all of which she promptly shot down. I clearly remember the first time she said ‘…hmmm, that isn’t obviously wrong…’—that was the start of our real collaboration. Bonnie: To be honest, the beginning of our collaboration was a bit frustrating. Ned was exuberant and loved learning biology and he was deeply committed to making a life-changing move in his research. Thus, he learned fast. I recall being fascinated by the physicists’ perspective and imagining how collaborating with Ned might transform our work, while grinding my teeth at the same time. He, as a newcomer to biology, did not have excellent taste in what problems to attack and he did not have a clue how hard it is to do experiments. He’d often propose that we whip out a mutant with tens of deletions or… I recall once saying, ‘You apparently think an orangutan can do what we do.’ On the other side, I had no math or physics since my freshman year of college and I could not solve a differential equation. Ned would explain how modeling or theory could provide us insight into questions and, initially, I could not comprehend how these equations delivered a change in our thinking. I’d need him to go over and over the equations and what each term meant. I recall him once standing at the chalkboard sort of looking 1
© 2014 IOP Publishing Ltd Printed in the UK
Phys. Biol. 11 (2014) 053010
Perspective
incredulous and saying, ‘Bonnie my 11 year old daughter Emma does math problems like these’. I said, ‘humor me’, and he went over it yet again. Together, this back and forth teaching allowed both of us to hone our skills in the other’s area of expertise, to find common problems that excited us, and to select areas to focus on, for which we could each contribute something unique toward a new understanding. Learning the fundamentals of the other’s discipline was, in my mind, the most difficult aspect. At that time, there were (essentially) no theorists hanging out in biology departments, and there were very few examples to show that our groups would profit scientifically from these conversations. I think one reason it worked is that Ned and I are curious about all kinds of science. We always felt we were learning something new from the other even if we had no outcome in mind, so we figured, what the heck, how could it hurt. Once we each ‘got’ the fundamentals of the other’s discipline, good ideas started coming rapidly and, more importantly, our capacity to be savvy in the other’s realm took off with a steep slope. We are now nearly equal players in all aspects of the projects: Ned in biology and I in theory. Ned: Working with Bonnie and her group has certainly been exciting for me, and has taken my group’s research in unexpected new directions. Bonnie studies quorum sensing, i.e. cell–cell communication in bacteria. The quorum-sensing system is intrinsically multiscale, spanning from signaling molecules to proteins (e.g. small molecule ligands, receptors, signaling intermediates, and transcription factors) and small regulatory RNAs to networks, and up to cells, communities, and entire ecosystems. Working together, we have been able to identify opportunities for modeling at all these scales, in particular modeling receptors from the perspective of statistical mechanics, analyzing signaling networks with ideas from information theory, and recently addressing communities of cells in biofilms via agent-based models. One of the great things about our long-term collaboration is that we have developed significant trust, both in terms of sharing information and in terms of respecting each other’s judgment and insights. This is definitely a twoway street, both with physicists contributing to experiments (and in many cases learning to do the experiments) and biologists suggesting directions and ideas for modeling, and indeed learning to develop the models themselves. Bonnie: One of the aspects of the collaboration that I find most exciting is the iterative nature of our theory-experiment setup. We do experiments, the data from which are used to refine the models, and in turn, the models can predict new biology and drive us to do experiments that we would not have done had we not been interacting with the biophysicists. One example that comes to mind is our discovery that the transcription factor called AphA is the master regulator of the quorum-sensing program when cells are at low cell density and acting as individuals. We had long known of the transcription factor called LuxR that controls the high cell density quorum-sensing gene expression cascade that enables cells to act as collectives. I recall Ned and his gang making models of the quorumsensing regulatory network, incorporating all of the known components, their regulatory roles, their copy numbers, their expression levels, their targets, feedback loops, rates and so on. At a certain point he kept coming by, very frustrated, saying his group could not recapitulate the circuit dynamics with the components and data we had provided them. He said, ‘You are missing a regulator that acts at low cell density.’ I was sort of put out by that. The physicist telling the geneticist she had not done a thorough job with her screens. I figured it was more likely that something was wrong with the parameters of the model. Luckily, the postdocs in my group were talking to the postdocs in Ned’s group on refining the model. One from my gang took the bait about the missing component, developed and carried out a screen to identify a low cell density regulator, and voila, AphA and a step-change in our understanding. Identification of AphA, beyond solving one mystery, provided us additional exciting 2
Phys. Biol. 11 (2014) 053010
Perspective
questions, and years of new work, both experimental and theoretical, became ours for exploration. Ned and Bonnie: One of the crucial ingredients for successful research at the interface of physics and biology is the merger of different perspectives. For example, we have weekly group meetings about quorum sensing involving the groups of five PIs: Bonnie, Ned, Fred Hughson (structural biology), Martin Semmelhack (organic chemistry), and Howard Stone (microfluidics). Our groups are all concentrated on the same problems, but each component group brings very different tools and approaches. The geneticists and molecular biologists immediately think of clever mutants and assays, the structural biologists go for mechanisms and analogy to known structures, the chemists think about 3D space and designing small molecule probes, the engineers wonder about the consequences of flow and rheology and microfluidics approaches, and the physicists conceive models and think about equations. We have some heady discussions, and the different perspectives add energy and excitement to the meetings. Often, someone will make a remark that is well known from the perspective of his or her field, but that is news to many others in the room. Sub-collaborations crop up and mini-projects are initiated under the umbrella of the overarching super-group structure. We highly recommend this kind of freewheeling interdisciplinary group discussion to any collaborators working at the interface of fields. Total immersion for everyone—from the undergraduates to the PIs is the key. Ned: I think I’ve learned a few general lessons for physicists about successful collaborations with biologists. First off, physicists have to learn the basic ideas and terminology in a field, and also learn how the relevant experiments are performed. This learning requires some investment, but it’s well worth it. Learning the basic ideas in some area of biology is not always as straightforward as it sounds. In many cases, there’s a great deal of conventional wisdom, based on experiments that everyone in the field knows. However, even if the experiments are sound, the interpretations that led to the conventional wisdom may not be correct. It is important for physicists to maintain a bit of skepticism. Knowing the terminology in a field is also important, to make it possible to read and understand the relevant literature and to converse accurately and efficiently with the biologists about technical issues. In my experience, biologists often have a good physical intuition for the phenomena they’re studying, but most do not express their ideas in standard physics terminology, so physicists need to learn to translate. Very important is knowing how experiments are executed. In biology, details of experimental protocol, strains, methods of data analysis, etc can have a big impact on results. It’s good for physicists to remember that even though an experiment may be designed to measure some particular property of cells, the cells are sensing, remembering, and responding to many other stimuli in their environment (after all that’s how they survive). For this reason, some ‘irrelevant’ detail of the experiment can have a telling effect on what’s measured. Biologists generally tend to be better than the physicists at understanding this aspect of the complexity of living systems, and thus appreciating the importance of appropriate controls and detailed protocols. Another, more encouraging, general lesson for physicists is that physics matters in biology. Evolution is a tinkerer and cells often discover physical solutions to their biological problems. It’s been a pleasing theme of my own research that many of the problems my group has tackled as pure biology problems have turned out to have a central physical component. Examples include signaling systems, where Ising-type models provide a good description for receptor–receptor interactions and where multiple distinct inputs influence signaling via additive contributions to a single free energy, enzyme regulation in metabolic networks that relies on cooperative polymerization, and cell-shape determination that requires both polymers and reaction-diffusion systems to span 3
Phys. Biol. 11 (2014) 053010
Perspective
the scale between proteins and cells. As biology continues its pursuit of deeper mechanistic understanding of complex, multicomponent systems, living systems will provide more fodder for physicists to study. Finally, it’s important for physicists not to be embarrassed to ask simple questions of their biologist colleagues. Personally, there’s no hope that I will ever know as much as my biologist collaborators like Bonnie about the organisms they study. However, I can leverage their expertise to stay on track in trying to accurately model their beloved systems. I have noticed that most biologists are reluctant to explain basic facts for fear of insulting the intelligence of their physics listeners, so it’s important to be proactive in asking questions. Bonnie: The reverse is also true. If the biologists hope not to waste the physicists’ time, and they want the models to inform their (the biologists’) understanding in significant ways, it is crucial that the biologists understand and hold the physicists’ accountable for why particular parameters are chosen, or why some features of a simplified system are incorporated into the model while others are omitted, etc. Thus, constant questioning from the biology point of view is essential. The biologists must not let their egos, or perhaps (I’m speaking for myself here) their lack of rigorous mathematical training to get in the way. It is always okay to ask the naïve question. I may not be able to come up with the equations, but if what and why are explained to me, I often have real insight into whether the biological entities represented by those equations are relevant and whether the modeling approach is on track or not. Ned and I have learned to ask as many questions as possible. This sets the tone for the group, shows that no question is too simple, and frequently leads to a change in thinking of the scientists in one or more of the disciplines in the room. We are lucky that our physics–biology collaboration is centered on cell–cell communication and collective activities. Thus, the members of the group, by virtue of the research project they have chosen, have made it part of their life’s work to define the principles underlying robust communication and successful collective activities. Thus, good communication and working together whether it is between quorum-sensing bacteria or the different scientists studying those critters is key. In the latter case, honest communication is the most essential component for a successful interdisciplinary collaboration. Being willing to be humbled by the complexity of living systems and to admit one’s ignorance in the face of nature’s awesomeness is an excellent place to start. Finally, I never planned to move from biology into physics. As Ned mentioned, we met randomly in a baggage claim and our collaboration started with Ned’s simple question (as I recall it), ‘Can I tag along with you to find the bus?’ Our shared curiosity has so far led to 15 years of friendship, collaboration, joint lab meetings, joint students and postdocs, joint manuscripts, joint grants, and labs located adjacent to one another. The success of this initial physics–biology venture opened our eyes to the thrill of interdisciplinary science. This realization led Ned and me to actively seek additional adventurous collaborators, who as described above, brought expertise in structure, chemistry, and most recently, engineering. My view of the group is that our collective imagination is our only limitation, not the gaps in each person’s formal training. By now, the students and postdocs are fearless about crossing disciplinary boundaries. They join the ‘super group’ specifically because of the exciting possibilities the interdisciplinary team provides to broaden their vision and to successfully attack questions far out of their individual comfort zones. This arrangement makes it so that every day each of us is challenged, in a friendly way, to be smarter. We, and our shared science, thrive in this atmosphere.
4
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Contact us
My IOPscience
Working together at the interface of physics and biology
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2014 Phys. Biol. 11 053010 (http://iopscience.iop.org/1478-3975/11/5/053010) View the table of contents for this issue, or go to the journal homepage for more Download details: IP Address: 130.133.8.114 This content was downloaded on 05/05/2017 at 08:25 Please note that terms and conditions apply.
You may also be interested in: Research at the interface of physics and biology: bridging the two fields Kamal Shukla A model for signal transduction during quorum sensing in Vibrio harveyi Suman K Banik, Andrew T Fenley and Rahul V Kulkarni Stochastic switching in biology: from genotype to phenotype Paul C Bressloff Statistical mechanics of tuned cell signalling: sensitive collective response by synthetic biological circuits M Voliotis and T B Liverpool Ask not what physics can do for biology—ask what biology can do for physics Hans Frauenfelder Transforming transportation David Smith
Physical Biology Phys. Biol. 11 (2014) 053010 (4pp)
doi:10.1088/1478-3975/11/5/053010
Perspective
Working together at the interface of physics and biology 1,2
Bonnie L Bassler and 2,3 Ned S Wingreen 1 Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544, USA 2 Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA 3 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA E-mail: [email protected]
1478-3975/14/053010+04$33.00
Abstract
Good communication, whether it is between quorum-sensing bacteria or the different scientists studying those critters, is the key to a successful interdisciplinary collaboration, Bonnie Bassler and Ned Wingreen provide a personal perspective on working at the interface between the physical and biological sciences. Keywords: interdisciplinary, physics, biology
Ned: My long-term collaboration with Bonnie began fortuitously when we met in the Mexico City airport baggage claim in 1999. We were both going to the BLAST (Bacterial Locomotion and Signal Transduction) Conference. My background is in theoretical condensed matter physics, and at that time my growing interest in biology was not accompanied by much actual knowledge. I recognized Bonnie as a Princeton University biologist, and since I was living in Princeton and working nearby at the NEC Research Institute, I summoned up my courage and introduced myself as a physicist trying to move into biology. Bonnie: Ned and I chatted as we walked to the bus that was taking participants to the conference. I, trying to be friendly, asked about his interest in the physics of two-component signaling systems (bacterial two-component proteins are the singular focus of the meeting). Ned said ‘What’s a two-component protein?’ I said (agog) ‘You better sit by me on the bus or you are going to have the worst week of your life’. We had an enjoyable two-hour tutorial on the way to the conference site, with many other biologists piping in over my shoulder to describe to Ned the basics in the field of bacterial signaling. Ned: What a great introduction to biology, and what an inspiration to learn more! By the end of the meeting, I felt I owed Bonnie some deep ‘physicist’s’ insight into bacterial quorum sensing. In an effort to fulfill this obligation, over the next two years, I regularly presented ideas to Bonnie, all of which she promptly shot down. I clearly remember the first time she said ‘…hmmm, that isn’t obviously wrong…’—that was the start of our real collaboration. Bonnie: To be honest, the beginning of our collaboration was a bit frustrating. Ned was exuberant and loved learning biology and he was deeply committed to making a life-changing move in his research. Thus, he learned fast. I recall being fascinated by the physicists’ perspective and imagining how collaborating with Ned might transform our work, while grinding my teeth at the same time. He, as a newcomer to biology, did not have excellent taste in what problems to attack and he did not have a clue how hard it is to do experiments. He’d often propose that we whip out a mutant with tens of deletions or… I recall once saying, ‘You apparently think an orangutan can do what we do.’ On the other side, I had no math or physics since my freshman year of college and I could not solve a differential equation. Ned would explain how modeling or theory could provide us insight into questions and, initially, I could not comprehend how these equations delivered a change in our thinking. I’d need him to go over and over the equations and what each term meant. I recall him once standing at the chalkboard sort of looking 1
© 2014 IOP Publishing Ltd Printed in the UK
Phys. Biol. 11 (2014) 053010
Perspective
incredulous and saying, ‘Bonnie my 11 year old daughter Emma does math problems like these’. I said, ‘humor me’, and he went over it yet again. Together, this back and forth teaching allowed both of us to hone our skills in the other’s area of expertise, to find common problems that excited us, and to select areas to focus on, for which we could each contribute something unique toward a new understanding. Learning the fundamentals of the other’s discipline was, in my mind, the most difficult aspect. At that time, there were (essentially) no theorists hanging out in biology departments, and there were very few examples to show that our groups would profit scientifically from these conversations. I think one reason it worked is that Ned and I are curious about all kinds of science. We always felt we were learning something new from the other even if we had no outcome in mind, so we figured, what the heck, how could it hurt. Once we each ‘got’ the fundamentals of the other’s discipline, good ideas started coming rapidly and, more importantly, our capacity to be savvy in the other’s realm took off with a steep slope. We are now nearly equal players in all aspects of the projects: Ned in biology and I in theory. Ned: Working with Bonnie and her group has certainly been exciting for me, and has taken my group’s research in unexpected new directions. Bonnie studies quorum sensing, i.e. cell–cell communication in bacteria. The quorum-sensing system is intrinsically multiscale, spanning from signaling molecules to proteins (e.g. small molecule ligands, receptors, signaling intermediates, and transcription factors) and small regulatory RNAs to networks, and up to cells, communities, and entire ecosystems. Working together, we have been able to identify opportunities for modeling at all these scales, in particular modeling receptors from the perspective of statistical mechanics, analyzing signaling networks with ideas from information theory, and recently addressing communities of cells in biofilms via agent-based models. One of the great things about our long-term collaboration is that we have developed significant trust, both in terms of sharing information and in terms of respecting each other’s judgment and insights. This is definitely a twoway street, both with physicists contributing to experiments (and in many cases learning to do the experiments) and biologists suggesting directions and ideas for modeling, and indeed learning to develop the models themselves. Bonnie: One of the aspects of the collaboration that I find most exciting is the iterative nature of our theory-experiment setup. We do experiments, the data from which are used to refine the models, and in turn, the models can predict new biology and drive us to do experiments that we would not have done had we not been interacting with the biophysicists. One example that comes to mind is our discovery that the transcription factor called AphA is the master regulator of the quorum-sensing program when cells are at low cell density and acting as individuals. We had long known of the transcription factor called LuxR that controls the high cell density quorum-sensing gene expression cascade that enables cells to act as collectives. I recall Ned and his gang making models of the quorumsensing regulatory network, incorporating all of the known components, their regulatory roles, their copy numbers, their expression levels, their targets, feedback loops, rates and so on. At a certain point he kept coming by, very frustrated, saying his group could not recapitulate the circuit dynamics with the components and data we had provided them. He said, ‘You are missing a regulator that acts at low cell density.’ I was sort of put out by that. The physicist telling the geneticist she had not done a thorough job with her screens. I figured it was more likely that something was wrong with the parameters of the model. Luckily, the postdocs in my group were talking to the postdocs in Ned’s group on refining the model. One from my gang took the bait about the missing component, developed and carried out a screen to identify a low cell density regulator, and voila, AphA and a step-change in our understanding. Identification of AphA, beyond solving one mystery, provided us additional exciting 2
Phys. Biol. 11 (2014) 053010
Perspective
questions, and years of new work, both experimental and theoretical, became ours for exploration. Ned and Bonnie: One of the crucial ingredients for successful research at the interface of physics and biology is the merger of different perspectives. For example, we have weekly group meetings about quorum sensing involving the groups of five PIs: Bonnie, Ned, Fred Hughson (structural biology), Martin Semmelhack (organic chemistry), and Howard Stone (microfluidics). Our groups are all concentrated on the same problems, but each component group brings very different tools and approaches. The geneticists and molecular biologists immediately think of clever mutants and assays, the structural biologists go for mechanisms and analogy to known structures, the chemists think about 3D space and designing small molecule probes, the engineers wonder about the consequences of flow and rheology and microfluidics approaches, and the physicists conceive models and think about equations. We have some heady discussions, and the different perspectives add energy and excitement to the meetings. Often, someone will make a remark that is well known from the perspective of his or her field, but that is news to many others in the room. Sub-collaborations crop up and mini-projects are initiated under the umbrella of the overarching super-group structure. We highly recommend this kind of freewheeling interdisciplinary group discussion to any collaborators working at the interface of fields. Total immersion for everyone—from the undergraduates to the PIs is the key. Ned: I think I’ve learned a few general lessons for physicists about successful collaborations with biologists. First off, physicists have to learn the basic ideas and terminology in a field, and also learn how the relevant experiments are performed. This learning requires some investment, but it’s well worth it. Learning the basic ideas in some area of biology is not always as straightforward as it sounds. In many cases, there’s a great deal of conventional wisdom, based on experiments that everyone in the field knows. However, even if the experiments are sound, the interpretations that led to the conventional wisdom may not be correct. It is important for physicists to maintain a bit of skepticism. Knowing the terminology in a field is also important, to make it possible to read and understand the relevant literature and to converse accurately and efficiently with the biologists about technical issues. In my experience, biologists often have a good physical intuition for the phenomena they’re studying, but most do not express their ideas in standard physics terminology, so physicists need to learn to translate. Very important is knowing how experiments are executed. In biology, details of experimental protocol, strains, methods of data analysis, etc can have a big impact on results. It’s good for physicists to remember that even though an experiment may be designed to measure some particular property of cells, the cells are sensing, remembering, and responding to many other stimuli in their environment (after all that’s how they survive). For this reason, some ‘irrelevant’ detail of the experiment can have a telling effect on what’s measured. Biologists generally tend to be better than the physicists at understanding this aspect of the complexity of living systems, and thus appreciating the importance of appropriate controls and detailed protocols. Another, more encouraging, general lesson for physicists is that physics matters in biology. Evolution is a tinkerer and cells often discover physical solutions to their biological problems. It’s been a pleasing theme of my own research that many of the problems my group has tackled as pure biology problems have turned out to have a central physical component. Examples include signaling systems, where Ising-type models provide a good description for receptor–receptor interactions and where multiple distinct inputs influence signaling via additive contributions to a single free energy, enzyme regulation in metabolic networks that relies on cooperative polymerization, and cell-shape determination that requires both polymers and reaction-diffusion systems to span 3
Phys. Biol. 11 (2014) 053010
Perspective
the scale between proteins and cells. As biology continues its pursuit of deeper mechanistic understanding of complex, multicomponent systems, living systems will provide more fodder for physicists to study. Finally, it’s important for physicists not to be embarrassed to ask simple questions of their biologist colleagues. Personally, there’s no hope that I will ever know as much as my biologist collaborators like Bonnie about the organisms they study. However, I can leverage their expertise to stay on track in trying to accurately model their beloved systems. I have noticed that most biologists are reluctant to explain basic facts for fear of insulting the intelligence of their physics listeners, so it’s important to be proactive in asking questions. Bonnie: The reverse is also true. If the biologists hope not to waste the physicists’ time, and they want the models to inform their (the biologists’) understanding in significant ways, it is crucial that the biologists understand and hold the physicists’ accountable for why particular parameters are chosen, or why some features of a simplified system are incorporated into the model while others are omitted, etc. Thus, constant questioning from the biology point of view is essential. The biologists must not let their egos, or perhaps (I’m speaking for myself here) their lack of rigorous mathematical training to get in the way. It is always okay to ask the naïve question. I may not be able to come up with the equations, but if what and why are explained to me, I often have real insight into whether the biological entities represented by those equations are relevant and whether the modeling approach is on track or not. Ned and I have learned to ask as many questions as possible. This sets the tone for the group, shows that no question is too simple, and frequently leads to a change in thinking of the scientists in one or more of the disciplines in the room. We are lucky that our physics–biology collaboration is centered on cell–cell communication and collective activities. Thus, the members of the group, by virtue of the research project they have chosen, have made it part of their life’s work to define the principles underlying robust communication and successful collective activities. Thus, good communication and working together whether it is between quorum-sensing bacteria or the different scientists studying those critters is key. In the latter case, honest communication is the most essential component for a successful interdisciplinary collaboration. Being willing to be humbled by the complexity of living systems and to admit one’s ignorance in the face of nature’s awesomeness is an excellent place to start. Finally, I never planned to move from biology into physics. As Ned mentioned, we met randomly in a baggage claim and our collaboration started with Ned’s simple question (as I recall it), ‘Can I tag along with you to find the bus?’ Our shared curiosity has so far led to 15 years of friendship, collaboration, joint lab meetings, joint students and postdocs, joint manuscripts, joint grants, and labs located adjacent to one another. The success of this initial physics–biology venture opened our eyes to the thrill of interdisciplinary science. This realization led Ned and me to actively seek additional adventurous collaborators, who as described above, brought expertise in structure, chemistry, and most recently, engineering. My view of the group is that our collective imagination is our only limitation, not the gaps in each person’s formal training. By now, the students and postdocs are fearless about crossing disciplinary boundaries. They join the ‘super group’ specifically because of the exciting possibilities the interdisciplinary team provides to broaden their vision and to successfully attack questions far out of their individual comfort zones. This arrangement makes it so that every day each of us is challenged, in a friendly way, to be smarter. We, and our shared science, thrive in this atmosphere.
4
