In recent years it has been fruitful to model the physical world in a categorical framework. In this talk I will give an outline of this process theoretic view with a particular focus on its applications to quantum mechanics and quantum computing. I will discuss how abstract categorical structure captures certain quantum protocols, such as teleportation, unearthing the topological nature of them, and how we can use algebraic structures internal to a category to develop a framework for circuit-based quantum computing in the form of the ZX-calculus.

As biological data has become more accessible and available in biology and healthcare, we find increasing opportunities to leverage artificial intelligence to help with data integration and picking out patterns in complex data. In this short talk, we will provide glimpses of what we do at the Novo Nordisk Research Centre Oxford towards understanding patient journeys, and in the use of knowledge graphs to draw insights from diverse biomedical data streams

Fibonacci numbers in plants, such as in sunflower spiral counts, have long fascinated mathematicians. For the last thirty years, most analyses have been variants of a Standard Model in which plant organs are treated as point nodes successively placed on a cylinder according to a given function of the previous node positions, not too close or too far away from the existing nodes. These models usually lead to lattice solutions. As a parameter of the model, like the diameter of the cylinder, is changed, the lattice can transition to another, more complex lattice, with a different spiral count. It can typically be proved that these transitions move lattice counts to higher Fibonacci numbers. While mathematically compelling, empirical validation of this Standard Model is as yet weak, even though the underlying molecular mechanisms are increasingly well characterised. 

In this talk I'll show a gallery of Fibonacci patterning and give a brief history of mathematical approaches, including a partially successful attempt by Alan Turing. I'll describe how the classification of lattices on cylinders connects both to a representation of $SL(2,Z)$ and to applications through defining the constraint that any model must satisfy to show Fibonacci structure. I'll discuss a range of such models, how they might be used to make testable predictions, and why this matters.

From 2011 to 2017 Jonathan Swinton  was a visiting professor to MPLS in Oxford in Computational Systems Biology. His new textbook Mathematical Phyllotaxis will be published  soon, and his Alan Turing's Manchester will be republished by The History Press in May 2022. 

 In addition, another class of cell-cell communication is by long, thin cellular protrusions that are ~100 microns (many cell-lengths) in length and ~100 nanometers (below traditional microscope resolution) in width. These protrusions have been recently discovered in many organisms, including nanotubes humans and airinemes in zebrafish. But, before establishing communication, these protrusions must find their target cell. Here we demonstrate airinemes in zebrafish are consistent with a finite persistent random walk model. We study this model by stochastic simulation, and by numerically solving the survival probability equation using Strang splitting. The probability of contacting the target cell is maximized for a balance between ballistic search (straight) and diffusive (highly curved, random) search. We find that the curvature of airinemes in zebrafish, extracted from live cell microscopy, is approximately the same value as the optimum in the simple persistent random walk model. We also explore the ability of the target cell to infer direction of the airineme’s source, finding the experimentally observed parameters to be at a Pareto optimum balancing directional sensing with contact initiation.

In collective navigation a population travels as a group from an origin to a destination. Famous examples include the migrations of birds and whales, between winter and summer grounds, but collective movements also extend down to microorganisms and cell populations. Collective navigation is believed to improve the efficiency of migration, for example through the presence of more knowledgeable individuals that guide naive members ("leader-follower behaviour") or through the averaging out of individual uncertainty ("many wrongs"). In this talk I will describe both individual and continuous approaches for modelling collective navigation. We investigate the point at which group information becomes beneficial to migration and how it can help a population navigate through areas with poor guidance information. We also explore the effectiveness of different modes through which a leader can herd a group of naïve followers. As an application we will consider the impact of noise pollution on the migration of whales through the North Sea.

My seminar will discuss various data-science issues related to
neurogenomics. First, I will focus on classic disorders of the brain,
which affect nearly a fifth of the world's population. Robust
phenotype-genotype associations have been established for several
psychiatric diseases (e.g., schizophrenia, bipolar disorder). However,
understanding their molecular causes is still a challenge. To address
this, the PsychENCODE consortium generated thousands of transcriptome
(bulk and single-cell) datasets from 1,866 individuals. Using these
data, we have developed interpretable machine learning approaches for
deciphering functional genomic elements and linkages in the brain and
psychiatric disorders. Specifically, we developed a deep-learning
model embedding the physical regulatory network to predict phenotype
from genotype. Our model uses a conditional Deep Boltzmann Machine
architecture and introduces lateral connectivity at the visible layer
to embed the biological structure learned from the regulatory network
and QTL linkages. Our model improves disease prediction (6X compared
to additive polygenic risk scores), highlights key genes for
disorders, and imputes missing transcriptome information from genotype
data alone. Next, I will look at the "data exhaust" from this activity
- that is, how one can find other things from the genomic analyses
than what is necessarily intended. I will focus on genomic privacy,
which is a main stumbling block in tackling problems in large-scale
neurogenomics. In particular, I will look at how the quantifications
of expression levels can reveal something about the subjects studied
and how one can take steps to sanitize the data and protect patient
anonymity. Finally, another stumbling block in neurogenomics is more
accurately and precisely phenotyping the individuals. I will discuss
some preliminary work we've done in digital phenotyping.

The morphogenesis of branched tissues has been a subject of long-standing interest and debate. Although much is known about the signaling pathways that control cell fate decisions, it remains unclear how macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Based on large-scale reconstructions of the mouse mammary gland and kidney, we show that statistical features of the developing branched epithelium can be explained quantitatively by a local self-organizing principle based on a branching and annihilating random walk (BARW). In this model, renewing tip-localized progenitors drive a serial process of ductal elongation and stochastic tip bifurcation that terminates when active tips encounter maturing ducts. Finally, based on reconstructions of the developing mouse salivary gland, we propose a generalisation of BARW model in which tips arrested through steric interaction with proximate ducts reactivate their branching programme as constraints become alleviated through the expansion of the underlying matrix. This inflationary branching-arresting random walk model presents a general paradigm for branching morphogenesis when the ductal epithelium grows cooperatively with the matrix into which it expands.

CRISPR is synonymous with a transformative genome editing technology that is innovating basic and applied sciences. I will report about the use of computational approaches to clarify the molecular basis and the gene-editing function of CRISPR-Cas9 and newly discovered CRISPR systems that are emerging as powerful tools for viral detection, including the SARS-CoV-2 coronavirus. We have implemented a multiscale approach, which combines classical molecular dynamics (MD) and enhanced sampling techniques, ab-initio MD, mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approaches and constant pH MD (CpH MD), as well as cryo-EM fitting tools and graph theory derived analysis methods, to reveal the mechanistic basis of nucleic acid binding, catalysis, selectivity, and allostery in CRISPR systems. Using a Gaussian accelerated MD method and the Anton-2 supercluster we determined the conformational activation of CRISPR-Cas9 and the selectivity mechanism against off-target sequences. By applying network models graph theory, we have characterized a mechanism of allosteric regulation, transferring the information of DNA binding to the catalytic sites for cleavages. This mechanism is now being probed in novel Anti-CRISPR proteins, forming multi-mega Dalton complexes with the CRISPR enzymes and used for gene regulation and control. CpH MD simulations have been combined with ab-initio MD and a mixed QM/MM approach to establish the catalytic mechanism of DNA cleavage. Finally, by using multi-microsecond MD simulations we have recently probed a mechanism of DNA-induced of activation in the Cas12a enzyme, which underlies the detection of viral genetic elements, including the SARS-CoV-2 coronavirus. Overall, our outcomes contribute to the mechanistic understanding of CRISPR-based gene-editing technologies, providing information that is critical for the development of improved gene-editing tools for biomedical applications.

Gastrulation is a critical event in vertebrate morphogenesis, characterized by coordinated large-scale multi-cellular movements. One grand challenge in modern biology is understanding how spatio-temporal morphological structures emerge from cellular processes in a developing organism and vary across vertebrates. We derive a theoretical framework that couples tissue flows, stress-dependent myosin activity, and actomyosin cable orientation. Our model, consisting of a set of nonlinear coupled PDEs, predicts the onset and development of observed experimental patterns of wild-type and perturbations of chick gastrulation as a spontaneous instability of a uniform state. We use analysis and numerics to show how our model recapitulates the phase space of gastrulation morphologies seen across vertebrates, consistent with experiments. Altogether, this suggests that early embryonic self-organization follows from a minimal predictive theory of active mechano-sensitive flows. 

 https://www.biorxiv.org/content/10.1101/2021.10.03.462928v2