Harold Fellermann

Newcastle University | NCL · School of Computing Science

DNA-based memory systems are being reported with increasing frequency. However, dynamic DNA data structures able to store and recall information in an ordered way, and able to be interfaced with external nucleic acid computing circuits, have so far received little attention. Here we present an in vitro implementation of a stack data structure using...

We present the Infobiotics Workbench (IBW), a user-friendly, scalable, and integrated computational environment for the computer-aided design of synthetic biological systems. It supports an iterative workflow that begins with specification of the desired synthetic system, followed by simulation and verification of the system in high-performance env...

We provide a practical construction to map (slightly modified) GOTO-programs to chemical reaction systems. While the embedding reveals that a certain small fragment of the chemtainer calculus is already Turing complete, the main goal of our ongoing research is to exploit the fact that we can translate arbitrary control-flow into real chemical syste...

Many complex behaviors in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is dif...

Many complex behaviours in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is di...

Synthetic biology uses living cells as the substrate for performing human-defined computations. Many current implementations of cellular computing are based on the “genetic circuit” metaphor, an approximation of the operation of silicon-based computers. Although this conceptual mapping has been relatively successful, we argue that it fundamentally...

Motivation: 3D physical modelling is a powerful computational technique that allows for the simulation of complex systems such as consortia of mixed bacterial species. The complexities in physical modelling reside in the knowledge intensive model building process and the computational expense in calculating their numerical solutions. These models...

Design of experiments (DOE) enables scientists to explore complex, multidimensional spaces against a background of experimental variability with the minimum of resource. While these methods are most successful when combined with expert knowledge to define the design space and capture the dimensionality of the problem, many scientists believe, often...

Data to support Data Availability Statement Harold Fellermann, Ben Shirt-Ediss, Jerzy W Koryza, Matthew Linsley, Dennis W Lendrem, John D Isaacs, Thomas J Howard 2019 Design of Experiments and the Virtual PCR Simulator: an online game for pharmaceutical scientists and biotechnologists. Pharmaceutical Statistics, In press.

Our PCR Simulator is a web-based application designed to introduce concepts of multi-factorial experimental design and support teaching of the polymerase chain reaction. Learners select experimental settings and receive results of their simulated reactions quickly, allowing rapid iteration between data generation and analysis. This enables the stud...

Motivation: 3D physical modelling is a powerful computational technique that allows for the simulation of complex systems such as consortia of mixed bacterial species. The complexities in physical modelling reside in the knowledge intensive model building process and the computational expense in calculating their numerical solutions. These models c...

We consider self-organization processes in networks of coupled chaotic maps whose dynamics determine the time evolution of the network's connectivity. In particular, a structural development rule is introduced that enhances the asymmetry of the influence that two nodes exert on each other. Our motivating assumption is that this rule can give rise t...

Autocatalytic sets are self-sustaining and collectively catalytic chemical reaction networks which are believed to have played an important role in the origin of life. Simulation studies have shown that autocatalytic sets are, in principle, evolvable if multiple autocatalytic subsets can exist in different combinations within compartments, i.e., so...

uthors and contributions as published: Jonathan Naylor, Harold Fellermann, Yuchun Ding, Waleed K. Mohammed, Nicholas S. Jakubovics, Joy Mukherjee, Catherine A. Biggs, Phillip C. Wright, and Natalio Krasnogor. JN wrote the manuscript, developed the software and models and performed data analysis. HF supervised the work, designed the overall study, s...

Template directed replication of nucleic acids is at the essence of all living beings and a major milestone for any origin of life scenario. We here present an idealized model of prebiotic sequence replication, where binary polymers act as templates for their autocatalytic replication, thereby serving as each others reactants and products in an int...

We recently reported the design for a DNA nano-device that can record and store molecular signals. Here we present an evolutionary algorithm tailored to optimising nucleic acid sequences that predictively fold into our desired target structures. In our approach, a DNA device is first specified abstractly: the topology of the individual strands and...

Simbiotics is a spatially explicit multi-scale modeling platform for the design, simulation and analysis of bacterial populations. Systems ranging from planktonic cells and colonies, to biofilm formation and development may be modeled. Representation of biological systems in Simbiotics is flexible, user-defined processes may be in a variety of form...

Nanotechnology and synthetic biology are rapidly converging, with DNA origami being one of the leading bridging technologies. DNA origami was shown to work well in a wide array of biotic environments. However, the large majority of extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus severely limiting its future applicabili...

Recent advances Synthetic Biology are ushering a new practical computational substrate based on programmable information processing via biological cells. Due to the difficulties in orchestrating complex programmes using myriads of relatively simple, limited and highly stochastic processors such as living cells, robust computational technology to sp...

We present an implementation of an in vitro signal recorder based on DNA assembly and strand displacement. The signal recorder implements a stack data structure in which both data as well as operators are represented by single stranded DNA " bricks ". The stack grows by adding push and write bricks and shrinks in last-in-first-out manner by adding...

We provide a non-equilibrium thermodynamic description of the life-cycle of a droplet based, chemically feasible, system of protocells. By coupling the protocells metabolic kinetics with its thermodynamics, we demonstrate how the system can be driven out of equilibrium to ensure protocell growth and replication. This coupling allows us to derive th...

Biological systems employ compartmentalization and other co-localization strategies in order to orchestrate a multitude of biochemical processes by simultaneously enabling “data hiding” and modularization. This article presents recent research that embraces compartmentalization and co-location as an organizational programmatic principle in syntheti...

We present a formal calculus, termed the chemtainer calculus, able to capture the complexity of compartmentalized reaction systems such as populations of possibly nested vesicular compartments. Compartments contain molecular cargo as well as surface markers in the form of DNA single strands. These markers serve as compartment addresses and allow fo...

Synthetic Biology aspires to design, compose and engineer biological systems that implement specified behaviour. When designing such systems, hypothesis testing via computational modelling and simulation is vital in order to reduce the need of costly wet lab experiments. As a case study, we discuss the use of computational modelling and stochastic...

An autocatalytic binary polymer system is studied as an abstract model for a chemical reaction network capable to evolve. Due to autocatalysis, long polymers appear spontaneously and their concentration is shown to be maintained at the same level as that of monomers. When the reaction starts from a pool of monomers, highly ordered populations with...

Biological systems employ compartmentalisation in order to orchestrate a multitude of biochemical processes by simultaneously enabling “data hiding” and modularisation. In this paper, we present recent research projects that embrace compartmentalisation as an organisational programmatic principle in synthetic biological and biomimetic systems. In t...

In this paper, we illustrate the use of the INFOBIOTICS WORKBENCH platform, designed to model and analyse stochastic P systems, by modelling basic synthetic Boolean gates and analysing them using some computational techniques: simulation, verification and biocompilation.

An autocatalytic pattern matching polymer system is studied as an abstract model for chemical ecosystem evolution. Highly ordered populations with particular sequence patterns appear spontaneously out of a vast number of possible states. The interplay between the selected microscopic sequence patterns and the macroscopic cooperative structures is e...

We propose an automaton, a theoretical framework that demonstrates how to improve the yield of the synthesis of branched chemical polymer reactions. This is achieved by separating substeps of the path of synthesis into compartments. We use chemical containers (chemtainers) to carry the substances through a sequence of fixed successive compartments....

Higher-order structures that originate from the specific and reversible DNA-directed self-assembly of microscopic building blocks hold great promise for future technologies. Here, we functionalized biotinylated soft colloid oil-in-water emulsion droplets with biotinylated single-stranded DNA oligonucleotides using streptavidin as an intermediary li...

We perform a spatially resolved simulation study of an AND gate based on DNA strand displacement using several lengths of the toehold and the adjacent domains. DNA strands are modelled using a coarse-grained dynamic bonding model {[}C. Svaneborg, Comp. Phys. Comm. 183, 1793 (2012){]}. We observe a complex transition path from the initial state to t...

biochemical information processing and production, supermolecular self-assembly, DNA computing, membrane computing, stochastic pi-calculus.

We study DNA self-assembly and DNA computation using a coarse-grained DNA model within the directional dynamic bonding framework {[}C. Svaneborg, Comp. Phys. Comm. 183, 1793 (2012){]}. In our model, a single nucleotide or domain is represented by a single interaction site. Complementary sites can reversibly hybridize and dehybridize during a simula...

Von Neumann, the inventor of the modern computer, realized that if life is a physical process, it should be possible to implement life in other media than biochemistry. In the 1950s, he was one of the first to propose the possibility of implementing genuine living processes in computers and robots. This perspective, while still controversial, is ra...

It is well known that non-enzymatic template directed molecular replicators X + nO ---> 2X exhibit parabolic growth d[X]/dt = k [X]^{1/2}. Here, we analyze the dependence of the effective replication rate constant k on hybridization energies, temperature, strand length, and sequence composition. First we derive analytical criteria for the replicati...

The creation of artificial cell-like entities – chemical systems that are able to self-replicate and evolve – requires the integration of containers, metabolism, and information. In this chapter, we present possible candidates for these subsystems and the experimental achievements made toward their replication. The discussion focuses on several sug...

When seeking to assemble minimal life from the bottom up in wet carbon chemistry, the critical properties of life apparently emerge from the interconnected functions of three subsystems: information, metabolism and container. Such interconnected supramolecular systems, so-called protocells, are under the right circumstances able to mimic the main f...

We propose a novel method to reduce the dimensionality of modular Boolean networks, in which an original network is represented by a coarse-grained representation. We analyzed the performance of the method by simulations of randomly wired modular Kauffman and activator-inhibitor networks with respect to reliability, determinism, and efficiency. It...

Dissipative particle dynamics DPD is now a well-established method for simulating soft matter systems. However, its applicability was recently questioned because some investigations showed an upper coarse-graining limit that would prevent the applicability of the method to the whole mesoscopic range. This article aims to re-establish DPD as a truly...

Although spatial structures can play a crucial role in chemical systems and can drastically alter the outcome of reactions, the traditional framework of artificial chemistry is a well-stirred tank reactor with no spatial representation in mind. Advanced method development in physical chemistry has made a class of models accessible to the realms of...

What is minimal life, how can we make it, and how can it be useful? We present experimental and computational results towards bridging nonliving and living matter, which results in life that is different and much simpler than contemporary life. A simple yet tightly coupled catalytic cooperation between genes, metabolism, and container forms the des...

The first comprehensive general resource on state-of-the-art protocell research, describing current approaches to making new forms of life from scratch in the laboratory. Protocells offers a comprehensive resource on current attempts to create simple forms of life from scratch in the laboratory. These minimal versions of cells, known as protocells,...

The first comprehensive general resource on state-of-the-art protocell research, describing current approaches to making new forms of life from scratch in the laboratory. Protocells offers a comprehensive resource on current attempts to create simple forms of life from scratch in the laboratory. These minimal versions of cells, known as protocells,...

The building of minimal self-reproducing systems with a physical embodiment (generically called protocells) is a great challenge, with implications for both theory and applied sciences. Although the classical view of a living protocell assumes that it includes information-carrying molecules as an essential ingredient, a dividing cell-like structure...

Cross-reactions and other systematic difficulties generated by the coupling of functional chemical subsystems pose the largest challenge for assembling a viable protocell in the laboratory. Our current work seeks to identify and clarify such key issues as we represent and analyze in simulation a full implementation of a minimal protocell. Using a 3...

Cross-reactions and other systematic issues generated by the coupling of functional chemical subsystems pose the largest challenge for assembling a viable protocell in the laboratory. Our current work seeks to identify and clarify such key issues as we represent and analyze in simulation a full implementation of a minimal protocell. Using a 3D diss...