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Frequently Asked Questions  (in no particular order)


What is the weird music on the main page?
        It is the opera version of "Spider Pig", from The Simpsons movie (used here in accordance with Title 17 U.S.C. Section 107, distributed without profit.
        "Spider pig, spider pig; does whatever a spiderpig does; can he swing from a rope? no he can't - he's a pig."

What does your lab work on?        
    Projects include:
            Understanding the role of cytoskeleton in the initiation of left-right asymmetry
            Understanding the role of ion channels/pumps in establishing bioelectric gradients during early left-right patterning
            Understanding how physiological gradients become transduced into asymmetric patterns of gene expression
            Understanding the role of specific ion currents in limb, tail, and craniofacial regeneration
            Learning to control bioelectric state of wound cells to promote regeneration of limbs, eyes, and other complex structures
            Understanding the role of brain and body asymmetry in non-lateralized behaviors (intelligence, recall, etc.)
            Understanding how bioelectric circuits control anatomical polarity and morphogenesis during planaria regeneration
            Analyzing the ability of tissues and cells outside the CNS to remember information and imprint it on the regenerating brain
            Understanding the bioelectric signatures (and control modalities) for neoplastic transformation (cancer)
            Understanding neurotransmitter and transmembrane potental control of stem cells by the host during morphogenesis
            Developing automated learning systems to allow high-throughput search for nootropic compounds

What ties it all together?
            We view biological systems from a cybernetic perspective: how do living structures acquire, store, and process information? Information comes in two flavors: spatial (morphological) and temporal (patterns in environmental signals). We address the former by asking how large-scale pattern formation is established, maintained, and regenerated against perturbations. We address the latter by asking how memories (learned information) are stored and transmitted by different types of biological structures.

What are some of the Big Questions you are addressing?
        How is consistent left-right asymmetry leveraged from subcellular (molecular) chirality onto multiple cell fields?
        How do organisms store the "target morphology" to which they repair during regeneration and morphostasis?
        Can cancer be understood as a disease of geometry (failure to attend to large-scale morphogenetic cues of the host)?
        How can we generate quantitative algorithmic models that go beyond pathways and allow us to predict (and rationally manipulate) shape?
        How are adult stem cells integrated into complex morphogenetic activity by the host context (3D patterning, beyond stem cell differentiation)?
        How are bioelectrical signals used to establish long-range patterning cues and how are these signals linked to transcription networks and biochemical pathways?
        What aspect of cellular function enables memory and what is the relationship between information processing and its tissue substratum?

Why do you work on so many things? Why not focus?
        These are the questions that keep me up at night!  As long as we're making progress, and no other lab is addressing the same workplan, we continue to push all of these fascinating directions. They seem to cover very different aspects of biology, but there may be fundamental connecting features underlying them all and that is the hypothesis that drives all of this work.

What's all this bioelectric stuff? What is bioelectricity and why not stick to well-known biochemical signals?
        Bioelectricity refers to signals carried by the voltage gradients, ion flows, and electric fields that all cells receive and emit. It has been known for over 100 years that all cells, not just excitable nerves and muscle, exhibit steady-state long-term bioelectrical activity, and that this activity appears to be instructive for cell guidance, wound healing, and regeneration. It has been abundantly show that these signals are not mere housekeeping physiology, but indeed serve to control proliferation, migration, and differentiation of cells.  Although an increasing number of microarray and other unbiased approaches have been turning up ion channels in such roles, the function of specific ion transport events in morphogenesis in vivo has only been scratched at the surface. The latest challenge has been to use the high-resolution powerful tools of molecular genetics to probe the functional roles of bioelectric signals in regeneration, development, and cancer and show how these signals integrate with the biochemical and genetic pathways familiar to modern cell biology.  We are fascinated by these signals because 1) they offer very different properties for use in morphogenesis than do chemical gradients, 2) they function as a biophysical epigenetic layer on top of well-studied pathways, 3) they often act as master regulators, inducing complex morphogenetic programs from relatively simple signals, and 4) they appear to be widely conserved as patterning signals and thus offer great opportunity as control points for regenerative medicine.

Which model systems do you use and why?
        We use Xenopus laevis embryos because they're ideal for physiological experiments and are amenable from the earliest stages of development.
        We use zebrafish because they are transparent, and offer transgenic technology as well as optical techniques in a rapidly-developing organism.
        We use chick embryos because their flat early blastoderm is a good model for most amniotes (including mammals) and are very accessible in ovo.
        We use planaria because they possess incredible regenerative ability, are smart (can learn, allowing memory and brain regeneration experiments
                in the same animal), and are a convenient system in which adult stem cell integration into morphogenetic events can be studied.

What techniques are used in the lab?
        Standard molecular biology - cloning, qPCR
        Developmental genetics - expression analysis, transgenesis, regeneration assays, pharmacological screens
        Cell Biology and biophysics - cell and tissue culture
        Biophysics and physiology - in vivo analysis of bioelectrical state via fluorescent reporter dyes
        Behavior analysis - automated, quantitative, parallelized training and tracking of model animals
        Mathematical modeling - computer simulation, symbolic model generation

Why are all the projects so unusual and the emphasis different from most of the mainstream work in the field?
        I am, fundamentally (and by training), a computer scientist and I suppose that's why my perspective on these questions is different.

What are the practical implications of your work?
        Our projects are basic research aimed at understanding fundamental mechanisms. However, once uncovered, these mechanisms suggest control points for biomedical intervention. Thus, our work suggests novel approaches to the detection, prevention, and repair of birth defects (especially involving the laterality of the heart and various internal organs), new diagnostic and treatment modalities for some types of cancers, approaches to induce regenerative repair of limbs, eyes, spinal cords, and face, and the discovery of new nootropic drugs (compounds that increase intelligence or improve memory for example).

Some things to think about

"What is number, that man may know it, and what is man, that he may know a number?" -- Warren McCulloch

"How wonderful that we have met with a paradox. Now we have some hope of making progress." -- Niels Bohr

"The man who cannot occasionally imagine events and conditions of existence that are contrary to the causal principle as he knows it will never enrich his science by the addition of a new idea." -- Max Planck

"You can recognize a pioneer by the arrows in his back." -- Beverly Rubik

"One of the methodological foundations of science lies in the avoidance of the most fundamental questions. It is characteristic of physics, as practiced nowadays, not to really ask what matter is, for biology not to really ask what life is, and for psychology not to really ask what soul is." -- C. F. Von Weizsaecker

"The exact sciences start from the assumption that in the end, it will always be possible to understand nature, even in every new field of experience, but that we may make no a priori assumption as to the meaning of 'understand'." -- Werner Heisenberg

"Tell me how you are searching and I will tell you what you are searching for." -- Ludwig Wittgenstein

"It has always been clear that we were not so deeply interested in the theory of any particular biological phenomenon for its own sake, but mainly in so far as it helps to a greater comprehension of the general character of the processes that go on in living as contrasted with non-living systems." -- C. H. Waddington

"Discovery consists of seeing what everybody has seen and thinking what nobody has thought." -- Albert von Szent-Gyorgyi

"Information is information, neither energy nor matter. No materialism that fails to take account of this can survive the present day." --Norbert Weiner

Artificial Life is the study of man-made systems that exhibit behaviors characteristic of natural living systems. It complements the traditional biological sciences concerned with the analysis of living organisms by attempting to synthesize life-like behaviors within computers and other artificial media. By extending the empirical foundation upon which biology is based _beyond_ the carbon-chain life that has evolved on Earth, Artificial Life can contribute to theoretical biology by locating life-as-we-know-it within the larger picture of life-as-it-could-be. -- Chris Langton

"Computer Science is no more about computers than astronomy is about telescopes." -- E. W. Dijkstra

"Should one wish to learn the methods of a conjurer, he might vainly watch the latter's customary repertoire, and, so long as everything went smoothly, might never obtain a clue to the mysterious performance, baffled by the precision of the manipulations and the complexity of the apparatus; if, however, a single error were made in any part or if a single deviation from the customary method should force the manipulator along an unaccustomed path, it would give the investigator an opportunity to obtain a part or the whole of the secret. Thus. ... it seems likely that through the study of the abnormal or unusual, some insight may be obtained into that mystery of mysteries, the development of an organism." -- H. H. Wilder, 1908

On the subject of applied vs. basic research (e.g., regenerative medicine vs. developmental biology vs. artificial life):

"The death of Archimedes by the hands of a Roman soldier is symbolical of a world-change of the first magnitude: the Greeks, with their love of abstract science, were superseded in the leadership of the European world by the practical Romans. The Romans were a great race, but they were cursed with the sterility which waits upon practicality. They did not improve upon the knowledge of their forefathers, and all their advances were confined to the minor technical details of engineering. They were not dreamers enough to arrive at new points of view, which could give a more fundamental control over the forces of nature. No Roman lost his life because he was absorbed in the contemplation of a mathematical diagram. -- Alfred North Whitehead