Workshop on Morphometrics, Morphogenesis and Mathematics

In Fall 2018, the CMSA will host a Program on Mathematical Biology, which aims to describe recent mathematical advances in using geometry and statistics in a biological context, while also considering a range of physical theories that can predict biological shape at scales ranging from macromolecular assemblies to whole organ systems.

The plethora of natural shapes that surround us at every scale is both bewildering and astounding – from the electron micrograph of a polyhedral virus, to the branching pattern of a gnarled tree to the convolutions in the brain. Even at the human scale, the   shapes seen in a garden at the scale of a pollen grain, a seed, a sapling, a root, a flower or leaf are so numerous that “it is enough to drive the sanest man mad,” wrote Darwin. Can we classify these shapes and understand their origins quantitatively?

In biology, there is growing interest in and ability to quantify growth and form in the context of the size and shape of bacteria and other protists, to understand how polymeric assemblies grow and shrink (in the cytoskeleton), and how cells divide, change size and shape, and move to organize tissues, change their topology and geometry, and link multiple scales and connect biochemical to mechanical aspects of these problems, all in a self-regulated setting.

To understand these questions, we need to describe shape (biomathematics), predict shape (biophysics), and design shape (bioengineering).

For example, in mathematics there are some beautiful links to Nash’s embedding theorem,  connections to quasi-conformal geometry, Ricci flows and geometric PDE, to Gromov’s h principle, to geometrical singularities and singular geometries, discrete and computational differential geometry, to stochastic geometry and shape characterization (a la Grenander, Mumford etc.). A nice question here is to use the large datasets (in 4D) and analyze them using ideas from statistical geometry (a la Taylor, Adler) to look for similarities and differences across species during development, and across evolution.

In physics, there are questions of generalizing classical theories to include activity, break the usual Galilean invariance, as well as isotropy, frame indifference, homogeneity, and create both agent (cell)-based and continuum theories for ordered, active machines, linking statistical to continuum mechanics, and understanding the instabilities and patterns that arise. Active generalizations of liquid crystals, polar materials, polymers etc. are only just beginning to be explored and there are some nice physical analogs of biological growth/form that are yet to be studied.  

The CMSA will be hosting a Workshop on Morphometrics, Morphogenesis and Mathematics from October 22-24 at the Center of Mathematical Sciences and Applications, located at 20 Garden Street, Cambridge, MA.

The workshop is organized by L. Mahadevan (Harvard), O. Pourquie (Harvard), A. Srivastava (Florida).

For a list of lodging options convenient to the Center, please visit our recommended lodgings page.

Videos of the talks

Confirmed Speakers:

Monday, October 22

Time Speaker Title/Abstract
8:30 – 9:00am Breakfast
9:00 – 9:15am Welcome and Introduction
Tutorial on Morphometrics
9:15 – 10:30 Anuj Srivastava Title: Shape Analysis of Functional Data

Abstract: This tutorial style presentation is on recent advances in functional and shape data analysis that emphasizes the following ideas: (1) Shapes of interest are represented by continuous objects (curves, surfaces, etc) rather than discrete representations of the past; (2) the registration problem, i.e. the correspondence of points across objects, considered a difficult problem in shape analysis, is handled during analysis rather then treated as pre-processing; and (3) the goal is to derive statistical inferences about shapes, relative to underlying probability distributions. The central idea is to choose metrics (or energies) with appropriate invariance properties and physical interpretations, and use them for analyzing shapes.

Additionally, one uses certain square-root representations to simplify these complex metrics into more standard mathematical tools, to enable implementation involving large datasets. I will motivate these ideas using a number of problems from biology, medical imaging, and computer vision.

10:30 – 10:45 Coffee Break
10:45 – 12:15 Sayan Mukherjee Title: Integral Geometry for Modeling Shapes
Abstract: We study transformations of shapes into representations that allow for analysis using standard statistical tools. The transformations are based on Euler integration and are of interest for their mathematical properties as well as their applications to science and engineering, because they provide a way of summarizing shapes in a topological, yet quantitative, way. By using an inversion theorem, we show that both transforms are injective on the space of shapes—each shape has a unique transform. By making use of a stratified space structure on the sphere, induced by hyperplane divisions, we prove additional uniqueness results in terms of distributions on the space of Euler curves. The main theoretical result provides the first (to our knowledge) finite bound required to specify any shape in certain uncountable families of shapes, bounded below by curvature. This result is perhaps best appreciated in terms of shattering number or the perspective that any point in these particular moduli spaces of shapes is indexed using a tree of finite depth. We also show how these transformations can be used in practice for medical imaging applications as well as for evolutionary morphology questions.
12:15 – 1:30 pm Lunch
1:30 – 2:15pm Jukka Jernvall Title: Bridging the gap between patterning and function

Abstract: Mammalian dentition is an organ system in which the basic patterning mechanisms are starting to be understood. Patterning, however, is not enough to produce a fully mature and functional organ. Growth, and especially in the case of organs such as the teeth, extracellular matrix secretion and mineralization are required before a tooth can function. Compared to patterning these final steps of organ formation are much less understood. In this talk I will discuss how the developmental shape, the result of patterning, maps to the functional shape or the mineralized enamel surface of the tooth. I will show how mathematical models on matrix secretion provide new tools and concepts to the study of development and evolution, and link work done on experimental species such as the mouse to evolutionary studies on the human lineage.

2:15 – 3:00pm Arkhat Abzhanov Title: Phylogenetic principles and morphogenetic mechanisms for evolvability and biological shape change


Abstract: Understanding the origins of morphological variation is one of the chief challenges to the modern biological sciences. Cranial diversity in vertebrates is a particularly inviting research topic as animal heads and faces show many dramatic and unique adaptive features which reflect their natural history. We aim to reveal molecular mechanisms underlying evolutionary processes that generate such morphological variation. To this purpose, we employ a synergistic combination of geometric morphometrics, comparative molecular embryology and functional experimentation methods to trace cranial evolution in reptiles, birds and mammals, some of the most charismatic animals on our planet. Our research is revealing how particular changes in developmental genetics can produce morphological alterations for natural selection to act upon, for example in generating adaptive radiations and morphological novelty.

3:00 – 3:30pm Coffee  Break
3:30 – 4:15pm Karen Sears Title: From genome to phenome: The developmental basis of mammalian variation

Abstract: Organismal form is the product of a complex suite of interacting developmental processes. Variation in these processes allows mammals to adapt to changing environments, but also generates congenital malformations in humans. Developmental variation therefore presents a unifying concept for evolutionary biology and biomedicine, whose understanding is critical to both fields. Our lab’s primary research goals are to determine how developmental variation interacts with environmental factors within a species to produce congenital malformations in humans, and among species to generate new evolutionary adaptations in mammals. To pursue these goals, we incorporate data from paleontology to mathematics to genomics to developmental biology to characterize developmental variation across biological scales, and interpret how this variation drives evolution and malformations in form. We also study multiple model and non-model mammals (e.g., mouse, bat, cat, deer, horse, pig, opossum). We use this approach to investigate multiple major topics including: mammalian limb evolution and development, major evolutionary transformations during mammalian evolution, mammalian sensory system evolution, the developmental basis of adaptive radiation. Results across these systems suggest that development’s important role in the “generation of the fittest” has shaped the distribution of intra-species variation and thereby the inter-species evolution of mammalian form.


Tuesday, October 23

Time Speaker Title/Abstract
8:30 – 9:00am Breakfast
Tutorial on Morphometrics (methods and applications)
9:00 – 10:30 am David Gu Title: Computational Conformal Geometry and Its Applications

Abstract: Computational conformal geometry is an interdisciplinary field, applying modern topology and geometry theories for engineering and medical applications. This talk covers the major theories, algorithms and applications of computational conformal geometry, such as discrete uniformization theorem, discrete surface Ricci flow algorithm and shape analysis.

10:30 – 11:00am Coffee Break
11:00 – 11:45pm Anjali Goswami Title: From Development to Deep Time: Phenomic Analysis of Tetrapod Cranial Integration and Evolution

Abstract: Phenotypic integration is a pervasive characteristic of organisms. Interactions among morphological traits, termed phenotypic integration, can be readily identified through quantitative analysis of geometric morphometric data from living and extinct organisms. These interactions have been hypothesized to reflect genetic, developmental, and functional relationships and to be a fundamental influence on morphological evolution on small to large time scales. Simulations using covariance matrices derived from landmark data for diverse vertebrate taxa confirm that trait integration can influence the trajectory and magnitude of response to selection. At a macroevolutionary scale, high phenotypic integration produces both more and less disparate organisms, and most often the latter, than would be expected under unconstrained evolution, thereby increasing morphological range, but also homoplasy and convergence. However, this effect may not translate simply to evolutionary rates.

While most large-scale studies of phenotypic integration and morphological evolution utilise relatively limited descriptors of morphology, such as lengths or a small set of homologous landmarks, surface sliding semi-landmark analysis allows for detailed quantification of complex 3D shapes, even across highly disparate taxa. We conducted the largest analysis to date of morphological evolution across diverse tetrapod clades using a dense dataset of landmarks and sliding semi-landmarks spanning the entire cranium and nearly 300 million years of evolution. Crania are highly modular, but this pattern varies across tetrapods. Modules also have disparate magnitudes of trait integration, which reflect developmental complexity in some, but not all clades. Tempo and mode are similarly highly variable, with some modules, such as the basicranium of birds, showing early bursts of shape evolution, while other regions, such as the rostrum, show sustained change throughout clade evolution. Leveraging this high density morphometric data, we further demonstrate that variation is unequally distributed across the cranium and that distinct patterns of variation characterize different tetrapod clades.

11:45 – 12:30 Siobhan Braybrook Title: The evolution and development of epidermal cell shape in plants
Abstract: The outer surfaces of leaves have been examined microscopically since microscopes were invented. The cell shapes presented by leaf epidermides can be diverse: from complex multi-cellular ‘hairs’ to flat tabular ‘pavement’ cells. We have recently begun to explore the diversity of pavement cell shape across the plant kingdom – with an eye towards understanding both how cell shapes are generated and what, if any, the function of shape might be. Using traditional morphometrics, in the first instance, we have found little phyllogenetic signal for cell shape in plant leaf epidermides. One of the interesting shape features in these cells is degree of margin undulation; solidity has been the best traditional morphometric to describe undulation thus far in our work. However, we are expanding our methods to include analysis of Total Absolute Curvature. Data examining periodic undulations in the maize leaf epidermis will be presented and explored. Further questions about cell shape in 3D will be presented as well.
12:30 – 2:00pm Lunch
2:00 – 2:45pm Eric Klassen Title: Comparing Shapes of Curves, Surfaces, and Higher Dimensional Immersions in Euclidean Space

Abstract: Comparing shapes and treating them as data for statistical analyses has many applications in biology and elsewhere. Certain elastic metrics on spaces of immersions have proved very effective for comparing curves and surfaces. The elastic metrics which have proved most useful for computation have been first order metrics, i.e., they compare tangent vectors to the shapes rather than points on the shapes. In this talk I will present a unifying view of these metrics, shedding new light on old methods and, I hope, suggesting new methods for analyzing surfaces and higher dimensional shapes.

2:45 – 3:30pm Laurent Younes Title: Estimation of Laminar Coordinate Systems between Two Surfaces.
Abstract: Given two disjoint open surfaces, we discuss the problem of estimating a parametrization (x,y,z) -> F(x,y,z) of an open subset of the three-dimensional space such that the set [z=0] corresponds to one of the surfaces, [z=1] to the other one, and for each t, (x,y) -> F(x,y,t) is an embedding onto the surface [z=t], with the additional constraint that the derivative of F with respect to t is always normal to this surface.The resulting construction is a natural way to build a foliation between the two surfaces for which the length of the transverse lines provides a good definition of thickness of the considered volume. It is designed with the objective of analyzing cortical volumes, for which a robust definition of thickness is essential for the characterization of degenerative diseases. Our estimation algorithm uses a version of the large deformation diffeomorphic metric mapping between surfaces in which normality constraints of the velocity field are enforced.The estimated coordinate system can also be used to estimate “cortical layers’’ as laminar segmentations of the inter-surface region that satisfy a local equi-volumetric condition called Bok’s hypothesis. Experimental results on human and feline brains will be presented as illustrations.This is joint work with Tilak Ratnanather, Sylvain Arguillere and Kwame Kutten.
3:30 – 4:00pm Coffee Break
4:00 – 4:45pm Cassandra Extavour Title: Insect egg evolution defies predicted allometric relationships across eight orders of magnitude in size

Abstract: Multicellular organisms commonly reproduce via a single-celled propagule, an egg. Egg size and shape relates to manyimportant developmental and life history processes, including maternal investment in reproduction, embryogenesis, progeny size, and fitness. Multiple mechanisms have been hypothesized to drive propagule size regulation and evolution. However, testing those hypotheses requires phenotypic shape data that varies over several orders of magnitude in size, from enough species to provide adequate statistical power, and with clear phylogenetic relationships allowing distinction between convergent and homologous sizes and shapes. To address these issues, we assembled a database of >10,000 morphological descriptions of eggs from over 6,000 unique species of the most speciose animal clade: the insects. This dataset represents, to our knowledge, the most diverse dataset of animal propagule sizes to date. We found that, contrary to published hypotheses, within insect lineages, egg size and shape have an isometric relationship. Furthermore, for any given adult size, egg volumes can range across four orders of magnitude. Larger eggs are generally more ellipsoidal, but allometric relationships vary significantly among lineages, and in Coleoptera (beetles) isometry is observed over seven orders of magnitude in egg size variation. In contrast to predicted allometric relationships between shape and size, egg shape for major lineages appears to have been determined early during insect evolution, and is conserved within lineages despite radical changes in size. We suggest that developmental parameters, including the relationship between egg size and developmental rate, will be critical in future models and analyses of propagule size evolution.

Samuel H. Church*, Seth Donoughe*, Bruno de Medeiros and Cassandra G. Extavour

* equal contribution


4:45 – 5:30pm Nipam Patel Title: The Cellular and Genetic Basis for Structural Color in Butterflies

Abstract: Research into the optical properties of structurally colored butterfly scales has been remarkably successful and revealed a great deal about the physical basis of color production in a myriad of species. Most of the studies are focused on adult scales, and often driven by the desire to eventually engineer these color-producing nanostructures using non-biological approaches. Our emphasis has been to understand how biological systems, in this case individual scale cells, are able to produce specific structures, particularly how these cells are able to pattern intracellular membranes and other cellular component to create the templates for the nanostructures. We have focused primarily on two systems.
1. Achillides (Peacock) swallowtails. We have investigated the developmental basis for the production of these scales by examining the cytoskeleton during pupal stages. We find that actin structures form as in any typical scale, but then undergo a remarkable reorganization to form a hexagonal array, which prefigure the eventual dimples. We are developing a number of live imaging techniques, combined with integration of fluorescent compounds used to monitor actin assembly, to understand how these hexagons are formed.
2. Structural color in the Buckeye, Junonia coenia. Most populations of Buckeyes have little or no blue or green coloration outside of the center of their eyespots. We are utilizing an artificial line that displays a stunning blue and green iridescence across large portions of the dorsal wings, which appears to be due to a simple thin film structure. We have begun a genetic mapping approach (Quantitative Trait Loci) to uncover the genetic basis for this structural color, and have shown that the optix gene plays a significant role in controlling the distribution of blue/green scales.

Wednesday, October 24

Time Speaker Title/Abstract
8:30 – 9:00am Breakfast
9:00 – 9:45am Peter Olver Title: Reassembly of broken objects

Abstract: The problem of reassembling broken objects appears in a broad range of applications, including jigsaw puzzle assembly, archaeology (broken pots and statues), surgery (broken bones and reassembly of histological sections), paleontology (broken fossils and egg shells), and anthropology (more broken bones). I will discuss recent progress on such problems, based on advances in the mathematical apparatus of equivalence, invariants, and symmetry, equivariant moving frames, differential and integral invariant signatures, and invariant numerical approximations.

9:45 – 10:30am Stephanie Pierce Title: Using morphometry to reveal macroevolutionary patterns

Abstract: My lab studies major transitions in vertebrate evolution through an analysis of the fossil record. A primary aim of our research is to quantify biological shape to reveal macroevolutionary patterns and to predict changes in functional performance and locomotor ecology. Here I will introduce two projects that have utilized morphometry as a central component of their methodological workflow. The first study focuses on the historic fish-to-tetrapod and associated water-to-land transition that occurred ~400-330 MYA and culminated in all modern-day terrestrial vertebrates. The second study investigates the “reptile”-to-mammal transition that occurred ~300-200 MYA and resulted in the most charismatic and ecology diverse group of animals alive today.

10:30 – 11:00am Coffee Break
11:00 – 11:45am Alain Trouve Title: Modular approaches and intrinsic metrics in diffeomorphometry
Abstract: The regular diffeomorphometric framework put the emphasis on induced Riemannian metrics on homogeneous spaces that are coming from right invariant metric on group of transformations. However, this extrinsic point of view on shape deformation costs (i.e. induced by extrinsic space deformation costs) can be challenged when prior information on objects properties is available. The very idea of deformation modules is to incorporate this prior knowledge into explicit shape dependent deformation constraints leading to a subriemannian point of view. However, since most of the prior knowledge is dealing with local properties of the infinitesimal strain tensor, this implies some interesting adaptation of the usual explicit framework leading to new intrinsic modules. Joint work with Barbara Gris
11:45 – 12:45 pm Olivier Pourquie & L. Mahadevan Summary and Discussion
12:45 – 2:00pm Lunch

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