Virtual

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.

Hierarchical stabilisation, allows us to define topological invariants for data starting from metrics to compare persistence modules. In this talk I will highlight the variety of metrics that can be constructed in an axiomatic way, via so called Noise Systems. The focus will then be on one invariant obtained through hierarchical stabilisation, the Stable Rank, which the TDA group at KTH has been studying in the last years. In particular I will address the problem of using this invariant on noisy and heterogeneous data. Lastly, I will illustrate the use of stable ranks on real data within a project on microglia morphology description, in collaboration with S. Siegert’s group, K. Hess and L. Kanari. 

The homogeneous coordinate ring of a projective variety may be constructed by geometrically quantizing the multiples of a symplectic form, using the complex structure as a polarization. In this talk, I will explain how a holomorphic Poisson structure allows us to deform the complex polarization into a generalized complex structure, leading to a non-commutative deformation of the homogeneous coordinate ring. The main tool is a conjectural construction of a category of generalized complex branes, which makes use of the A-model of an associated symplectic groupoid. I will explain this in the example of toric Poisson varieties. This is joint work with Marco Gualtieri (arXiv:2108.01658).

TBA

The curve graph of a surface of finite type is a fundamental object in the study of its mapping class group both from the metric and the combinatorial point of view. I will discuss joint work with Valentina Disarlo and Thomas Koberda where we conduct a thorough study of curve graphs from the model theoretic point of view, with particular emphasis in the problem of interpretability between different curve graphs and other geometric complexes.   

Donaldson-Thomas (DT) theory is an enumerative theory which produces a virtual count of stable coherent sheaves on a Calabi-Yau 3-fold. Motivic Donaldson-Thomas theory, originally introduced by Kontsevich-Soibelman, is a categorification of the DT theory. This categorification contains more refined information of the moduli space. In this talk, I will explain the role of d-critical locus structure in the definition of motivic DT invariant, following the definition by Bussi-Joyce-Meinhardt. I will also discuss results on this structure on the Hilbert schemes of zero dimensional subschemes on local toric Calabi-Yau threefolds. This is based on joint works with Sheldon Katz. The results have substantial overlap with recent work by Ricolfi-Savvas, but techniques used here are different. 

Dolbeault hypertoric manifolds are hyperkahler integrable systems generalizing the Ooguri-Vafa space. They approximate the Hitchin fibration near a totally degenerate nodal spectral curve. On the other hand, Betti hypertoric varieties are smooth affine varieties parametrizing microlocal sheaves on the same nodal spectral curve. I will review joint work with Zsuzsanna Dansco and Vivek Shende (arXiv:1910.00979) which constructs a diffeomorphism between the Dolbeault and Betti hypertorics, and proves that it intertwines the perverse and weight filtrations on their cohomologies. I will describe our main tool : deletion-contraction sequences arising from either smoothing a node of the spectral curve or separating its branches. I will also discuss some more recent developments and open questions.

In the search for a complete description of quantum mechanical and
gravitational phenomena, we are inevitably led to consider observables on
boundaries at infinity. This is the common mantra that there are no local
observables in quantum gravity and gives rise to the tantalising possibility
of a purely boundary--or holographic--description of physics in the
interior. The AdS/CFT correspondence provides an important working example
of these ideas, where the boundary description of quantum gravity in anti-de
Sitter (AdS) space is an ordinary quantum mechanical system-- in particular,
a Lorentzian Conformal Field Theory (CFT)--where the rules of the game are
well understood. It would be desirable to have a similar level of
understanding for the universe we actually live in. In this talk I will
explain some recent efforts that aim to understand the rules of the game for
observables on the future boundary of de Sitter (dS) space. Unlike in AdS,
the boundaries of dS space are purely spatial with no standard notion of
locality and time. This obscures how the boundary observables capture a
consistent picture of unitary time evolution in the interior of dS space. I

will explain how, despite this difference, the structural similarities
between dS and AdS spaces allow to forge relations between boundary
correlators in these two space-times. These can be used to import
techniques, results and understanding from AdS to dS.

I will discuss 3d N=4 supersymmetric gauge theories compactified on an elliptic curve, and how this set-up physically realises recent mathematical results on the equivariant elliptic cohomology of symplectic resolutions. In particular, I will describe the Berry connection for supersymmetric ground states, and in doing so connect the elliptic cohomology of the Higgs branch with spectral data of doubly periodic monopoles. I will show that boundary conditions, via a consideration of boundary ’t Hooft anomalies, naturally represent elliptic cohomology classes. Finally, if I have time, I will discuss mirror symmetry/symplectic duality in our framework, and physically recover concepts in elliptic cohomology such as the mother function, and the elliptic stable envelopes of Aganagic-Okounkov.

This talk will be based on https://arxiv.org/abs/2109.10907 with Mathew Bullimore.