TY - THES
AB - Social insect colonies tend to have numerous members which function together like a single organism in such harmony that the term ``super-organism'' is often used. In this analogy the reproductive caste is analogous to the primordial germ
cells of a metazoan, while the sterile worker caste corresponds to somatic cells. The worker castes, like tissues, are
in charge of all functions of a living being, besides reproduction. The establishment of new super-organismal units
(i.e. new colonies) is accomplished by the co-dependent castes. The term oftentimes goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation, nutrient regulation and gas exchange of a social insect colony. Furthermore, we assert that the super-organism has an immune system, and benefits from ``social immunity''.
Social immunity was first summoned by evolutionary biologists to resolve the apparent discrepancy between the expected high frequency of disease outbreak amongst numerous, closely related tightly-interacting hosts, living in stable and microbially-rich environments, against the exceptionally scarce epidemic accounts in natural populations. Social
immunity comprises a multi-layer assembly of behaviours which have evolved to effectively keep the pathogenic enemies of a colony at bay. The field of social immunity has drawn interest, as it becomes increasingly urgent to stop
the collapse of pollinator species and curb the growth of invasive pests. In the past decade, several mechanisms of
social immune responses have been dissected, but many more questions remain open.
I present my work in two experimental chapters. In the first, I use invasive garden ants (*Lasius neglectus*) to study how pathogen load and its distribution among nestmates affect the grooming response of the group. Any given group of ants will carry out the same total grooming work, but will direct their grooming effort towards individuals
carrying a relatively higher spore load. Contrary to expectation, the highest risk of transmission does not stem from grooming highly contaminated ants, but instead, we suggest that the grooming response likely minimizes spore loss to the environment, reducing contamination from inadvertent pickup from the substrate.
The second is a comparative developmental approach. I follow black garden ant queens (*Lasius niger*) and their colonies from mating flight, through hibernation for a year. Colonies which grow fast from the start, have a lower chance of survival through hibernation, and those which survive grow at a lower pace later. This is true for colonies of naive
and challenged queens. Early pathogen exposure of the queens changes colony dynamics in an unexpected way: colonies from exposed queens are more likely to grow slowly and recover in numbers only after they survive hibernation.
In addition to the two experimental chapters, this thesis includes a co-authored published review on organisational
immunity, where we enlist the experimental evidence and theoretical framework on which this hypothesis is built,
identify the caveats and underline how the field is ripe to overcome them. In a final chapter, I describe my part in
two collaborative efforts, one to develop an image-based tracker, and the second to develop a classifier for ant
behaviour.
AU - Casillas Perez, Barbara E
ID - 6435
KW - Social Immunity
KW - Sanitary care
KW - Social Insects
KW - Organisational Immunity
KW - Colony development
KW - Multi-target tracking
SN - 2663-337X
TI - Collective defenses of garden ants against a fungal pathogen
ER -
TY - THES
AB - Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory.
The recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes.
Finally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression.
AU - Cepeda Humerez, Sarah A
ID - 6473
KW - Information estimation
KW - Time-series
KW - data analysis
SN - 2663-337X
TI - Estimating information flow in single cells
ER -
TY - THES
AB - Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation.
Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify
a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate
a program governing migration steps important for both development and cancer metastasis.
AU - Valosková, Katarina
ID - 6546
SN - 2663-337X
TI - The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration
ER -
TY - THES
AB - The first part of the thesis considers the computational aspects of the homotopy groups πd(X) of a topological space X. It is well known that there is no algorithm to decide whether the fundamental group π1(X) of a given finite simplicial complex X is trivial. On the other hand, there are several algorithms that, given a finite simplicial complex X that is simply connected (i.e., with π1(X) trivial), compute the higher homotopy group πd(X) for any given d ≥ 2.
However, these algorithms come with a caveat: They compute the isomorphism type of πd(X), d ≥ 2 as an abstract finitely generated abelian group given by generators and relations, but they work with very implicit representations of the elements of πd(X). We present an algorithm that, given a simply connected space X, computes πd(X) and represents its elements as simplicial maps from suitable triangulations of the d-sphere Sd to X. For fixed d, the algorithm runs in time exponential in size(X), the number of simplices of X. Moreover, we prove that this is optimal: For every fixed d ≥ 2,
we construct a family of simply connected spaces X such that for any simplicial map representing a generator of πd(X), the size of the triangulation of S d on which the map is defined, is exponential in size(X).
In the second part of the thesis, we prove that the following question is algorithmically undecidable for d < ⌊3(k+1)/2⌋, k ≥ 5 and (k, d) ̸= (5, 7), which covers essentially everything outside the meta-stable range: Given a finite simplicial complex K of dimension k, decide whether there exists a piecewise-linear (i.e., linear on an arbitrarily fine subdivision of K) embedding f : K ↪→ Rd of K into a d-dimensional Euclidean space.
AU - Zhechev, Stephan Y
ID - 6681
SN - 2663-337X
TI - Algorithmic aspects of homotopy theory and embeddability
ER -
TY - THES
AB - Hybrid automata combine finite automata and dynamical systems, and model the interaction of digital with physical systems. Formal analysis that can guarantee the safety of all behaviors or rigorously witness failures, while unsolvable in general, has been tackled algorithmically using, e.g., abstraction, bounded model-checking, assisted theorem proving.
Nevertheless, very few methods have addressed the time-unbounded reachability analysis of hybrid automata and, for current sound and automatic tools, scalability remains critical. We develop methods for the polyhedral abstraction of hybrid automata, which construct coarse overapproximations and tightens them incrementally, in a CEGAR fashion. We use template polyhedra, i.e., polyhedra whose facets are normal to a given set of directions.
While, previously, directions were given by the user, we introduce (1) the first method
for computing template directions from spurious counterexamples, so as to generalize and
eliminate them. The method applies naturally to convex hybrid automata, i.e., hybrid
automata with (possibly non-linear) convex constraints on derivatives only, while for linear
ODE requires further abstraction. Specifically, we introduce (2) the conic abstractions,
which, partitioning the state space into appropriate (possibly non-uniform) cones, divide
curvy trajectories into relatively straight sections, suitable for polyhedral abstractions.
Finally, we introduce (3) space-time interpolation, which, combining interval arithmetic
and template refinement, computes appropriate (possibly non-uniform) time partitioning
and template directions along spurious trajectories, so as to eliminate them.
We obtain sound and automatic methods for the reachability analysis over dense
and unbounded time of convex hybrid automata and hybrid automata with linear ODE.
We build prototype tools and compare—favorably—our methods against the respective
state-of-the-art tools, on several benchmarks.
AU - Giacobbe, Mirco
ID - 6894
TI - Automatic time-unbounded reachability analysis of hybrid systems
ER -