Richard Gordon

Diatom Milking: A Review and New Approaches

The rise of human populations and the growth of cities contribute to the depletion of natural resources, increase their cost, and create potential climatic changes. To overcome difficulties in supplying populations and reducing the resource cost, a search for alternative pharmaceutical, nanotechnology, and energy sources has begun. Among the alternative sources, microalgae are the most promising because they use carbon dioxide (CO2) to produce biomass and/or valuable compounds. Once produced, the biomass is ordinarily harvested and processed (downstream program). Drying, grinding, and extraction steps are destructive to the microalgal biomass that then needs to be renewed. The extraction and purification processes generate organic wastes and require substantial energy inputs. Altogether, it is urgent to develop alternative downstream processes. Among the possibilities, milking invokes the concept that the extraction should not kill the algal cells. Therefore, it does not require growing the algae anew. In this review, we discuss research on milking of diatoms. The main themes are (a) development of alternative methods to extract and harvest high added value compounds; (b) design of photobioreactors; (c) biodiversity and (d) stress physiology, illustrated with original results dealing with oleaginous diatoms.

The organelle of differentiation in embryos: the cell state splitter.

The cell state splitter is a membraneless organelle at the apical end of each epithelial cell in a developing embryo. It consists of a microfilament ring and an intermediate filament ring subtending a microtubule mat. The microtubules and microfilament ring are in mechanical opposition as in a tensegrity structure. The cell state splitter is bistable, perturbations causing it to contract or expand radially. The intermediate filament ring provides metastability against small perturbations. Once this snap-through organelle is triggered, it initiates signal transduction to the nucleus, which changes gene expression in one of two readied manners, causing its cell to undergo a step of determination and subsequent differentiation. The cell state splitter also triggers the cell state splitters of adjacent cells to respond, resulting in a differentiation wave. Embryogenesis may be represented then as a bifurcating differentiation tree, each edge representing one cell type. In combination with the differentiation waves they propagate, cell state splitters explain the spatiotemporal course of differentiation in the developing embryo. This review is excerpted from and elaborates on “Embryogenesis Explained” (World Scientific Publishing, Singapore, 2016).

Toy models for macroevolutionary patterns and trends

Many models have been used to simplify and operationalize the subtle but complex mechanisms of biological evolution. Toy models are gross simplifications that nevertheless attempt to retain major essential features of evolution, bridging the gap between empirical reality and formal theoretical understanding. In this paper, we examine thirteen models which describe evolution that also qualify as such toy models, including the tree of life, branching processes, adaptive ratchets, fitness landscapes, and the role of nonlinear avalanches in evolutionary dynamics. Such toy models are intended to capture features such as evolutionary trends, coupled evolutionary dynamics of phenotype and genotype, adaptive change, branching, and evolutionary transience. The models discussed herein are applied to specific evolutionary contexts in various ways that simplify the complexity inherent in evolving populations. While toy models are overly simplistic, they also provide sufficient dynamics for capturing the fundamental mechanism(s) of evolution. Toy models might also be used to aid in high-throughput data analysis and the understanding of cultural evolutionary trends. This paper should serve as an introductory guide to the toy modeling of evolutionary complexity.

A cell state splitter and differentiation wave working-model for embryonic stem cell development and somatic cell epigenetic reprogramming.

Cell fate determination and development is a biology question that has yet to be fully answered. During embryogenesis and in vivo stem cell differentiation, cells/tissues deploy epigenetic mechanisms to accomplish differentiation and give rise to the fully developed organism. Although a biochemistry description of cellular genetics and epigenetics is important, additional mechanisms are necessary to completely solve the problem of embryogenesis, especially differentiation and the spatiotemporal coordination of cells/tissues during morphogenesis. The cell state splitter and differentiation wave working-model was initially proposed to explain the homeostatic primary neural induction in amphibian embryos. Here the model is adopted to explain experimental findings on in vitro embryonic stem cell, pluripotency and differentiation. Moreover, since somatic cells can be reverted to a stem-cell-like pluripotent state through the laboratory procedure called epigenetic reprogramming, erection of a cell state splitter could be a key event in their successful reprogramming. Overall, the cell state splitter working-model introduces a bistable cytoskeletal mechanism that partially explains cell fate determination and biological development. It offers an interdisciplinary framework that bridges the gap between molecular epigenetics and embryogenesis.

Metabolic engineering of TiO2 nanoparticles in Nitzschia palea to form diatom nanotubes: an ingredient for solar cells to produce electricity and biofuel

Diatoms are natures nanobot because they can be described as cells in a glass house. Three-dimensional nanobio-engineered frustules of diatoms have vast applications in nanomaterials and bio-photonics. The amorphous silica of diatom frustules is not a good semiconductor, but when coated with titanium dioxide (TiO2), the semiconducting efficiency of the frustules becomes adequate for use in numerous device applications, including solar cells. The metabolic incorporation of titanium dioxide nanoparticles in the diatom frustules is primarily used for the construction of titanium nanotubes. In the present study, TiO2 was metabolically inserted by a two-stage cultivation process and its incorporation in the diatom frustules was studied by spectroscopic and atomic force microscopic methods. It was found that diatom frustules metabolically inserted with nanostructured TiO2 by a two-stage cultivation in f/2 medium could replace nanostructured surface doping with titanium in dye-sensitized solar cells for heat and electricity production. The DSSC made from the titanium-doped diatom frustule has a power efficiency almost double (9.45%) that of the simple DSSC (4.20%) without any diatom frustule metabolically inserted with TiO2. Alternatively, these nanoarray diatom containing tubes may also be used for the construction of novel dye-sensitized solar cells, which may help in oozing lipids from living diatom cells, such as in algal cells, for the generation of an electric current.

Quantifying Mosaic Development: Towards an Evo-Devo Postmodern Synthesis of the Evolution of Development via Differentiation Trees of Embryos.

Embryonic development proceeds through a series of differentiation events. The mosaic version of this process (binary cell divisions) can be analyzed by comparing early development of Ciona intestinalis and Caenorhabditis elegans. To do this, we reorganize lineage trees into differentiation trees using the graph theory ordering of relative cell volume. Lineage and differentiation trees provide us with means to classify each cell using binary codes. Extracting data characterizing lineage tree position, cell volume, and nucleus position for each cell during early embryogenesis, we conduct several statistical analyses, both within and between taxa. We compare both cell volume distributions and cell volume across developmental time within and between single species and assess differences between lineage tree and differentiation tree orderings. This enhances our understanding of the differentiation events in a model of pure mosaic embryogenesis and its relationship to evolutionary conservation. We also contribute several new techniques for assessing both differences between lineage trees and differentiation trees, and differences between differentiation trees of different species. The results suggest that at the level of differentiation trees, there are broad similarities between distantly related mosaic embryos that might be essential to understanding evolutionary change and phylogeny reconstruction. Differentiation trees may therefore provide a basis for an Evo-Devo Postmodern Synthesis.

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three‐dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self‐organize into tissue‐specific structures given a correct in vitro environment. This proposition is supported by the generation of neo‐organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue‐engineering strategies may be conceptualized for generating self‐organizing transplants. Copyright

Information Isometry Technique Reveals Organizational Features in Developmental Cell Lineages

In this paper, we will introduce a method for calculating and visualizing the information content of embryogenesis called the information isometry technique. We treat cell lineage trees as directed acyclic graphs (DAGs) that can be subject to reordering using various criteria. When we compare alternative orderings of these graphs, they reveal subtle patterns of information. We use one such alternative criteria (e.g. a differentiation code) to sort cells at each level of the tree. Both axial- and differentiation-based orderings can by characterized using a binary classifier to quantify the order of particular cells at each level of a given tree. We calculate a Hamming distance to compare these orderings and reveal differences that result from these ordering criteria. We also introduce a method of visualization through the construction of isometric graphs, or a series of colored points forming isometric lines with each representing a level of the original lineage tree. We show that these graphs reveal biologically significant patterns through comparisons between randomly generated lineage/differentiation trees and the Caenorhabditis elegans lineage/differentiation tree. As a collective indicator of distance between various cell lineage orderings, isometric graphs can reveal a number of emergent patterns within cell lineages and between sublineages, including the relative information content of specific subtrees. These patterns of information content reveal the informative nature of alternative ordering criteria with respect to important trends in development.

CT brush and CancerZap!: two video games for computed tomography dose minimization

BackgroundX-ray dose from computed tomography (CT) scanners has become a significant public health concern. All CT scanners spray x-ray photons across a patient, including those using compressive sensing algorithms. New technologies make it possible to aim x-ray beams where they are most needed to form a diagnostic or screening image. We have designed a computer game, CT Brush, that takes advantage of this new flexibility. It uses a standard MART algorithm (Multiplicative Algebraic Reconstruction Technique), but with a user defined dynamically selected subset of the rays. The image appears as the player moves the CT brush over an initially blank scene, with dose accumulating with every “mouse down” move. The goal is to find the “tumor” with as few moves (least dose) as possible.ResultsWe have successfully implemented CT Brush in Java and made it available publicly, requesting crowdsourced feedback on improving the open source code. With this experience, we also outline a “shoot ‘em up game” CancerZap! for photon limited CT.ConclusionsWe anticipate that human computing games like these, analyzed by methods similar to those used to understand eye tracking, will lead to new object dependent CT algorithms that will require significantly less dose than object independent nonlinear and compressive sensing algorithms that depend on sprayed photons. Preliminary results suggest substantial dose reduction is achievable.

DevoWorm: data-theoretical synthesis of C. elegans development.

The DevoWorm group adds an important dimension to the OpenWorm Foundation9s goal of creating a digital nematode. Compared with the great diversity and plasticity found across the tree of life, Caenorhabditis elegans development is a rather unique model system. C. elegans biology provides us with a highly-deterministic developmental cell lineage, and a clear linkage from zygote to cells of the adult phenotype. This paper provides an example of the DevoWorm approach, merging computational modeling and insights from data science. The first part introduces alternative ways of understanding the embryo, including the role of hierarchical differentiation and whole-embryo pattern generation. We suggest that systematic decomposition of embryo feature space is just as important to understanding the embryo as single-gene and molecular studies. The second half of this paper focuses on the process of developmental cell terminal differentiation, and how terminally-differentiated cells contribute to structure and function of the adult phenotype. An analysis is conducted for cells that were present during discrete time intervals covering 200 to 400 minutes of embryogenesis, providing us with basic statistics on the tempo of the embryogenetic process in addition to the appearance of specific cell types and their order relative to embryogenetic time. As with ideas presented in the first section, these data may also provide clues as to the timing for the initial onset of stereotyped and autonomic behaviors of the developing animal. Taken together, these overlapping approaches can provide critical links across life-history, anatomy and function to reveal the essential components needed to create a complex digital organism, where artificial life imitates real life.Biological development is often described as a dynamic, emergent process. This is evident across a variety of phenomena, from the temporal organization of cell types in the embryo to compounding trends that affect large-scale differentiation. To better understand this, we propose combining quantitative investigations of biological development with theory-building techniques. This provides an alternative to the gene-centric view of development: namely, the view that developmental genes and their expression determine the complexity of the developmental phenotype. Using the model system Caenorhabditis elegans, we examine time-dependent properties of the embryonic phenotype and utilize the unique life-history properties to demonstrate how these emergent properties can be linked together by data analysis and theory-building. We also focus on embryogenetic differentiation processes, and how terminally-differentiated cells contribute to structure and function of the adult phenotype. Examining embryogenetic dynamics from 200 to 400 minutes post-fertilization provides basic quantitative information on developmental tempo and process. To summarize, theory construction techniques are summarized and proposed as a way to rigorously interpret our data. Our proposed approach to a formal data representation that can provide critical links across life-history, anatomy and function.