Derek Raine

A Fission-Fusion Origin for Life

To develop a comprehensive ‘cells-first’ approach to the origin of life, we propose that protocells form spontaneously and that the fission and fusion of these protocells drives the dynamics of their evolution. The fitness criterion for this evolution is taken to be the the stability (conservation) of domains in the protocellular membrane as determined by non-covalent molecular associations between the amphiphiles of the membrane and a subset of the macromolecules in the protocell. In the presence of a source of free energy the macromolecular content of the protocell (co-)evolves as the result of (domain-dependent) membrane-catalysed polymerisation of the prebiotic constituents delivered to the protocell by fusion. The metabolism of the cell therefore (co-)evolves on a rugged fitness landscape. We indicate how domain evolution with the same fitness criterion can potentially give rise to coding. Membrane domains may therefore provide the link between protocells and the RNA/DNA-world.

Hypothesis: hyperstructures regulate initiation in Escherichia coli and other bacteria

Hyperstructures or modules have been proposed to constitute a level of organisation intermediate between macromolecules and whole cells. In this model of intracellular organisation, hyperstructures compete and collaborate for existence within the membrane and cytoplasm. Those directly involved in the cell cycle include initiation, replication and division hyperstructures based on DnaA, SeqA and the 2-minute cluster, respectively. During the run-up to initiation, the mass to DNA ratio increases and, we contend, differential gene expression leads to some hyperstructures becoming more active and stable than others. This results in a drop in the diversity of hyperstructures, some of which release DnaA as they dissociate, and a DnaA-initiation hyperstructure forms. Subsequent DNA replication and cell division generate different daughter cells containing different hyperstructures. This has the advantage of increasing the phenotypic diversity of the population. In developing this model, we also invoke hyperstructures in the partitioning of origins of replication.

Hyperstructures, genome analysis and I-Cells

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

A new introductory quantum mechanics curriculum

The Institute of Physics New Quantum Curriculum consists of freely available online learning and teaching materials (quantumphysics.iop.org) for a first course in university quantum mechanics starting from two-level systems. This approach immediately immerses students in inherently quantum-mechanical aspects by focusing on experiments that have no classical explanation. It allows from the start a discussion of the interpretive aspects of quantum mechanics and quantum information theory. This paper gives an overview of the resources available from the IOP website. The core text includes around 80 articles which are co-authored by leading experts, arranged in themes, and can be used flexibly to provide a range of alternative approaches. Many of the articles include interactive simulations with accompanying activities and problem sets that can be explored by students to enhance their understanding. Much of the linear algebra needed for this approach is included in the resource. Solutions to activities are available to instructors. The resources can be used in a variety of ways, from being supplemental to existing courses to forming a complete programme.

Problem-based learning in astrophysics

Problem-based learning (PBL) can be integrated into the curriculum in many different ways. We compare three examples of PBL in undergraduate astrophysics programmes, and discuss the strengths and weaknesses of the various approaches.

Question 7: The First Units of Life Were Not Simple Cells

Five common assumptions about the first cells are challenged by the pre-biotic ecology model and are replaced by the following propositions: firstly, early cells were more complex, more varied and had a greater diversity of constituents than modern cells; secondly, the complexity of a cell is not related to the number of genes it contains, indeed, modern bacteria are as complex as eukaryotes; thirdly, the unit of early life was an ‘ecosystem’ rather than a ‘cell’; fourthly, the early cell needed no genes at all; fifthly, early life depended on non-covalent associations and on catalysts that were not confined to specific reactions. We present here the outlines of a theory that connects findings about modern bacteria with speculations about their origins.

The correlation between architecture and mRNA abundance in the genetic regulatory network of Escherichia coli.

BackgroundTwo aspects of genetic regulatory networks are the static architecture that describes the overall connectivity between the genes and the dynamics that describes the sequence of genes active at any one time as deduced from mRNA abundances. The nature of the relationship between these two aspects of these networks is a fundamental question. To address it, we have used the static architecture of the connectivity of the regulatory proteins of Escherichia coli to analyse their relationship to the abundance of the mRNAs encoding these proteins. In this we build on previous work which uses Boolean network models, but impose biological constraints that cannot be deduced from the mRNA abundances alone.ResultsFor a cell population of E. coli, we find that there is a strong and statistically significant linear dependence between the abundance of mRNA encoding a regulatory protein and the number of genes regulated by this protein. We use this result, together with the ratio of regulatory repressors to promoters, to simulate numerically a genetic regulatory network of a single cell. The resulting model exhibits similar correlations to that of E. coli.ConclusionThis analysis clarifies the relationship between the static architecture of a regulatory network and the consequences for the dynamics of its pattern of mRNA abundances. It also provides the constraints on the architecture required to construct a model network to simulate mRNA production.

Open Questions on the Origin of Life (OQOL).

The papers in this collection record the talks given at the conference on “Open Questions on the Origin of Life” held in Leicester in May 2012. This was the third such meeting in a series inspired by Professor Luisi with the agenda to discuss open problems and new approaches. The format of the papers presented here broadly keeps to that of the conference, with the extended abstracts of the talks followed by comments from other delegates, which capture just some of the lively discussions. Prior to the meeting the community is asked to submit questions for each of the conference sessions which are then chosen by ballot. In fact, the main characteristic of this kind of meeting is to collect those questions in the field of the origin of life which are not yet answered. Thus, while most of the conventional science meetings emphasize the new achievements, and ignore the points of ignorance, our meeting dwells precisely on the” dark side”, more in particular on the reasons why certain questions remain unsolved, and occasionally even ignored in the scientific discussion—and we try to understand why this is so, possibly looking for ways to come out of the impasse. This is not the place to summarise the individual questions or contributions but some of what seemed to us to be key themes did emerge. The largest group of contributions were identified by their authors as concerning the transition from chemistry to biology, perhaps because this can be interpreted as simply another way of posing the origin-of-life question in general terms, which is not quite the intention of these meetings. But one specific issue is whether we need new conceptual Orig Life Evol Biosph (2012) 42:379–383 DOI 10.1007/s11084-012-9298-x

Networks as constrained thermodynamic systems

We show how a network of interconnections between nodes can be constructed to have a specified distribution of nodal degrees. This is achieved by treating the network as a thermodynamic system subject to constraints and then rewiring the system to maintain the constraints while increasing the entropy. The general construction is given and illustrated by the simple example of an exponential network. By considering the constraints as a cost function analogous to an internal energy, we obtain a characterisation of the correspondence between the intensive and extensive variables of the network. Applied to networks in living organisms, this approach may lead to macroscopic variables useful in characterising living systems.

Determining the cosmological parameters from the linewidths of active galaxies

We have previously shown that the linewidth distribution in AGN can be accounted for by an axisymmetric broad emission line region. In this paper we show that the linewidth distribution changes with redshift and that these changes are dependent on H0 and q0. We show that relatively small samples of AGN at high redshift with measured linewidth at half maximum can be used to distinguish between values of H0 and q0. Furthermore larger low redshift samples can be used to distinguish between luminosity functions and hence different models of quasar evolution.