Theoretical physics and applied mathematics

Introduction | Theoretical work is necessary for the proper interpretation of data, for modelling biological systems, for the understanding of the physical phenomena exploited for sensing applications and for engineering the optimal detection systems. Fundamental questions that can be addressed with theoretical work are, for instance: which is the information content of images in fluorescence microscopy? How many photons are required to correctly estimate a fluorescence lifetime? In recent years, I worked to use biophysical imaging techniques as a tool for systems biology of cancer. The next big theoretical question I wish to address is: how biochemical networks encode for cellular decisions and maintain functional states? To address this question, we will have to develop accurate models of our data and the biology under study.

Recent and ongoing theory-based projects

All our projects require some modelling efforts and specialized data analysis. However, we have a few projects that are specifically focused on the theoretical aspects of the physics or biology we are studying. Here, a brief and incomplete summary of these projects:

  • Paracrine oncogenesis. We are investigating how cell-to-cell communication plays a role in the earliest steps during oncogenesis. Our first work is publicly available as a preprint [BIORXIV/2018/431478]. We hypothesise that cell-to-cell communication not only plays an important role during the early steps in oncogenesis but it is also essential to establish and maintain tumour heterogeneity.
  • Machine-learning. We have recently established a small team of people working on machine-learning algorithms to establish data pipelines that could make our advanced imaging tools accessible to an increasing number of laboratories. At the same time, these novel computational tools will be utilized to better understand our complex data.
  • Optogenetics. The capability to trigger biochemical reactions by genetically encoded probes is permitting us to perform better and less invasive single cell biochemical assays. We are investigating theoretical aspects of optogenetics, specifically for activation of CRE recombinase, that might enable us to develop better assays. Our aim is to seed oncogenic mutations in a well-defined spatiotemporal way, so to study the earliest behaviour of mutant cells within a three-dimensional tissue.

 


Milestones

Over the last few years, we have developed several theoretical models. A detailed description of some of the milestones is available on separate posts (click on links).

[coming up: clonal dynamics in the presence of DNA damage and clonal dynamics of interacting cells]

  • Photon-partitioning theorem: definition and optimization of biochemical resolving power in fluorescence microscopy (~2013)
  • High (super?) resolution volume rendering of confocal data (~2010)
  • Quantifying analyte concentrations by FRET imaging and phasor transforms (~2007)
  • Maximization of photon-economy and acquisition throughput in FLIM applications
  • Lifetime Moment Analysis (LiMA): graphical representations and missing analytical solutions for FLIM analysis in the frequency domain

 

Theory Pipeline

Other descriptions are in preparation (Maximization of photon-economy and acquisition throughput in FLIM applications; Simple analysis of lifetime images by linear transforms), follow me on twitter for updates.