The Enlightening Ramray Bhat: Origin Of Body Plans

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Stuart Newman and Ramray Bhat: Physical Biology, "Dynamical patterning modules: physico-genetic determinants of morphological development"

Earlier stories in this series:

• Stuart Newman, The New Master Of Evolution?
• Stuart Newman's "High Tea"


• Theory of Form to Evolution Center Stage


• Altenberg! The Woodstock of Evolution?


• "Altenberg 16" Evolution Summit


• Richard Dawkins Renounces Darwinism As Religion

Ramray Bhat

“Our theory does not stand against natural selection in its entirety – it relegates it to a less important role,” says Ramray Bhat, cell biologist Stuart Newman’s co-author of the just published paper in Physical Biology: “Dynamical patterning modules: physico-genetic determinants of morphological development”. Nevertheless, Neo-Darwinians – to whom natural selection is central to evolution – have tended to bury their heads in the sand when presented with a theory for form, which the Neo-Darwinian model lacks. Why spoil next year’s commercial celebration of the 150th anniversary of Charles Darwin’s Origin of Species for a really coherent new theory?

I asked Ramray Bhat, now a graduate student at New York Medical College, if he’d answer a few questions about his paper and tell me about his journey from Calcutta to Valhalla and a collaboration with Stuart Newman. Our conversation follows.

Suzan Mazur: Are you and your distinguished co-author Stuart Newman saying that you have the first really coherent theory of evolution with regard to how virtually all of today’s animal forms self-organized –35 phyla – roughly a half billion years ago?

Ramray Bhat: I would rather put it as follows -- we have the first really coherent framework to explain the origination and evolution of body plans and organ forms within a short evolutionary period, known as the Cambrian explosion.

Within this framework we also explore the relationships between gene products mediating the physics of biological matter (which we denote as DPMs) and transcription factors (DTFs), which carry out effects of the former within cells and tissues and hardwire DPMs’ molecular players within regulatory networks. This framework also solves the Molecular Homology-Analogy paradox -- why same/similar sets of genes are employed to build functionally or structurally similar organ forms in widely divergent organisms.

All of these are inconsistent with and cannot be explained by the classical Neo-Darwinian model. We accommodate the role of natural selection in our framework mainly to lock the already-emerged but immensely plastic forms into place, and to render them robust.

Suzan Mazur: How do you define self-organization?

Ramray Bhat: By self-organization we mean the generic property of biological matter to attain a certain complexity in size, shape and pattern without depending on a blueprint or a recipe that is coded within its genome, or for that matter any other “ome”. Rather this property comes from the physics and chemistry that make up biological matter

Suzan Mazur: You state that you take a physicalist perspective. And you identify a “pattern language” that shaped multicellular life as it emerged from the single-cell state at the time of the Cambrian explosion. You call this language DPMs – dynamical patterning modules. The concept of DPMs is the main thrust of your paper just published online in Physical Biology, correct?

Ramray Bhat: Correct. While the paper published in Physical Biology has been written with emphasis on the physics and physical phenomena that DPMs embody, our contribution to the International Journal of Developmental Biology explores in some depth the relationship of DPMs with DTFs.

We also believe that the forms preceding the Cambrian explosion need not have been necessarily single-celled. They might have been transiently and variably multicellular sheets. Diverse three-dimensional “plastic” (i.e., polymorphic) body plans came about within a short evolutionary period as a consequence of the DPMs acting singly or in combination with each other.

Suzan Mazur: You identify nine DPMs but say there are possibly more, as well as illustrate their effects. Are you saying in your paper that DPMs still exist? That while DPMs explored the formation of internal body cavities, segmentation, appendages, primitive hearts and eyes in highly plastic ancient multicellular organisms, DPMs continue to have a role in modern-day organisms – though only to a degree?

Ramray Bhat: Of course, DPMs continue to have a prominent role in the development of extant multicellular organisms. My experimental research involves trying to tease out the DPMs involved in patterning the skeleton of limbs. However, the DPMs can no longer explore as many new possibilities in terms of organ forms or body plans as they did in the ancient past; that is because their effects are now hardwired to the genome through millions of years of stabilizing evolution. The result of stable body plans and organ forms has come with a trade-off: the ability of the DPMs to freely explore what we call the morphospace is severely constrained.

Suzan Mazur: Why did you decide not to present a model for DPMs?

Ramray Bhat: Our first task was to build a theoretical framework within which to resolve issues that loom large in the field of evo-devo, such as the Cambrian explosion and the Molecular Homology-Analogy paradox. This framework was built by assimilating previous research in this area by Prof Newman and his colleagues. Having put forward the same in the form of these two papers, we would embark on our next step shortly -- to devise a computational model of the action of the DPMs.

Suzan Mazur: What do DPMs look like?

Ramray Bhat: DPMs per se are not readily visualizable like, say, proteins or genes, which are particular kinds of molecules. Each DPM consists of gene products and the physics they mobilize. For example the DPM we annotate as ADH consists of cadherins and lectins and their associated physical property of adhesion. These DPMs were present in unicellular organisms but assumed their physical role (relevant to rapid and exhaustive exploration of multicellular form), only in the context of multicellularity. The effects of DPMs are easy to visualize, however, and we have done so in a series of “before” and “after” figures in our Physical Biology paper.

Suzan Mazur: You identify DTFs – developmental transcription factors – as coming into play as stabilizers but only after considerable body-building took place in the multicellular organisms at the time of the Cambrian explosion. Could you say a bit more about the role of DTFs?

Ramray Bhat: Developmental biologists have observed a small set of genes, coordinating organismal development, to be highly conserved across the multicellular kingdom. They call these genes the Developmental Genetic Toolkit. The genes whose products constitute DPMs (along with the physical phenomena they mediate individually, and in combination) are components of this toolkit.

There is another class of molecular players which also figure in the Toolkit but are not tied to any physics per se. They act in consequence to the action of DPMs to switch on and off certain genes and thus mediate cell-specific or tissue-specific effects of the DPMs. Since the DTFs are as ancient as the DPM Toolkit components, they had roles in the unicellular world in mediating transcriptional responses to internal and external signals.

Since embryonic regions and organs did not come into existence before multicellularity, the association of the DTFs with the DPMs as well as with their own biological effects can be regarded more as “frozen accidents”. They may also have been the reason for a somewhat constrained genotype-phenotype relationship in extant organisms as they hardwire the DPMs by participating with them in regulatory networks.

Suzan Mazur: As a graduate student, does your experimental work in Stuart Newman’s laboratory have anything to do with the DPM theory you have put forward in the two papers?

Ramray Bhat: An underlying theme in Prof Newman’s lab has been to not only study the molecular players involved in a developmental phenomena and to tease out their dynamics, but also to understand the physics that goes along with their role. I investigate the pattern formation of limb skeleton -- the underlying principles of which are ubiquitous in the vertebrate kingdom. A lot of the molecules and their dynamics involved in this process such as cadherins, galectins, morphogens and the Notch pathway molecules are components of the very DPMs we have described in the paper. Using a cell-culture model, I am trying to pin down a core network of molecules patterning the process of cartilage formation in chicken limb buds.

Suzan Mazur: Do you expect resistance to your theory in light of all the celebration surrounding the 150th anniversary next year of Darwin's publication of the Origin of Species?

Ramray Bhat: Science takes place through a continual process of dialectics. We expect resistance and debate from the scientific community regarding these new ideas, as it is only through this that a collective understanding of the origination and evolution of organismal form can be bettered. Our theory does not stand against natural selection in its entirety -- it relegates it to a less important role -- one of fine-tuning and building upon the body plans and organ forms, brought about by actions and interactions of DPMs.

Suzan Mazur: How did you find your way from Calcutta to Valhalla and into Stuart Newman’s lab and collaboration on a paper he has said reflects a synthesis of twenty years of his work?

Ramray Bhat: I developed an interest in evolution while in high school and studied organismal development and embryology during my first year in medicine at the University of Calcutta Medical College. This interest grew into a passion and alongside the drudgery of my medical curriculum I was largely teaching myself evo-devo through the works of Stephen Gould, Stuart Kauffman, Mary Jane West-Eberhard and Wallace Arthur.

During this period, I was immensely encouraged to learn more and guided to a great extent by prominent scientists in India such as Prof Vidyanand Nanjundiah, Prof Partha Majumder and Prof Amitabh Joshi. It is through them that I came to know about the contributions in this field by Prof Newman.

Prof Newman’s theoretical-cum-experimental approach to research on limb skeletal pattern formation, his formidable contribution to the growth of the evo-devo field, as well as his attention to the socio-cultural and philosophical aspects of biological research motivated me to apply to New York Medical College.

The inspiration to co-write this paper largely came about through continuous discussions with Prof Newman as well as a long-held desire to resolve the above-mentioned evo-devo issues, which had been needling me ever since I started reading about evolution.

Suzan Mazur: How long have you been working with Stuart Newman?

Ramray Bhat: I have been working under him as a graduate student for the past two and a half years.

Suzan Mazur: How would you describe your collaboration with Stuart Newman?

Ramray Bhat: I would qualify my experience under him as more of an education than collaboration. Not only has my experimental research in his lab been stimulating, our daily, and sometimes into the night discussions on my research as well as biological theory and philosophy, which I feel is integral to an ideal scientific education, will go a long way in forging a meaningful and productive career, for me, in natural sciences.

Suzan Mazur: When will you complete your PhD, and will you stay in the US or return to India following your studies?

Ramray Bhat: I expect to complete my PhD within the next two years. I haven’t really thought about a next step, as I want to concentrate on the present, which is actually a fantastic period of my scientific life. However, I feel strongly about imbibing all that I can from this scientific environment and country and returning to India where I can contribute in a meaningful way to Indian science, research and education.

Suzan Mazur says her interest in evolution began with a Cessna single engine flight into Olduvai Gorge, across a closed Kenyan-Tanzanian border, to interview the late paleoanthropologist Mary Leakey. Their meeting followed discovery of the 3.5 million year old hominid footprints by Leakey and her team at Laetoli http://en.wikipedia.org/wiki/Laetoli. Mazur says Leakey was the only reason the Tanzanian authorities agreed to give landing clearance. Her reports have since appeared in the Financial Times, The Economist, Forbes, Newsday, Philadelphia Inquirer, Archaeology, Connoisseur, Omni and others, as well as on PBS, CBC and MBC. She has been a guest on McLaughlin, Charlie Rose and various Fox Television News programs. Email: sznmzr@aol.com

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