Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 22, 2025

One goal of synthetic biology is to provide well-characterised biological parts that behave predictably in genetic assemblies. To achieve this, each part must be characterised a time-resolved manner under relevant conditions. Robotic platforms can used automate this task and sufficiently large reproducible data sets including provenance. Although robotics significantly speed up the collection process, collation analysis resulting data, needed reprogram refine workflows for future iterations, often manual process. As result, even times rapidly advancing artificial intelligence, common design-build-test-learn (DBTL) cycle still not circular without human intervention. move towards fully automated DBTL cycles, we developed software framework enable robotic platform autonomously adjust test parameters. This interdisciplinary work between computer science thus transforms static into dynamic one. The includes components such as an importer retrieves measurement from platform’s devices writes it database. followed by optimizer selects next points based on balance exploration exploitation. shown able automatically optimize inducer concentration Bacillus subtilis system combination feed release Escherichia coli system. target product readily measurable green fluorescent reporter protein (GFP) produced over multiple, consecutive iterations testing. An evaluation chosen (learning) algorithms single dual factor optimization was performed. In article, share lessons learned development, implementation execution cycles platform.

Язык: Английский

Evolving concepts of the protein universe

iScience, Год журнала: 2025, Номер 28(3), С. 112012 - 112012

Опубликована: Фев. 14, 2025

The protein universe is the collection of all proteins on earth from organisms both extant and extinct. Classical studies folding suggested that exist as a unique three-dimensional conformation dictated by genetic code critical for function. In this perspective, we discuss ideas developments emerged over past three decades regarding structure-function paradigm. It now clear ordered (active/functional) disordered/denatured (and hence inactive/non-functional) represent continuum states rather than binary states. Some can switch folds without sequence change. Others conformational ensembles lacking defined structure yet play roles in many biological processes, including forming membrane-less organelles driven liquid-liquid phase separation. Numerous diverse harbor segments with potential to form amyloid fibrils, which are functional, some possess prion-like properties enabling conformation-based transfer heritable information. Taken together, these reveal remarkable complexity universe.

Язык: Английский

Cell shape noise strength regulates shape dynamics during EMT-associated cell spreading

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 15, 2024

ABSTRACT Cellular shape is intimately linked to cell function and state, transitions between states are tightly coupled changes. Yet, has been largely overlooked in state studies. Here, we combine morphometric analysis with theoretical modeling molecular perturbations interrogate dynamics during epithelial-to-mesenchymal transition (EMT). Using stochastic inference, extract the morphogenetic landscape underlying EMT. We show that within this landscape, EMT-associated spreading reflects a attractors. Strikingly, observe peak noise strength concomitant spreading, higher accelerates Our framework will be widely applicable quantitative investigations physiology disease. Together, our results identify key role for cellular stochasticity as regulator of change rates, highlight yield rich phenotypic information enhance understanding states.

Язык: Английский