Section: Research Program
Research Program
The recent advent of an increasing number of new microscopy techniques giving access to high throughput screenings and micro or nano-metric resolutions provides a means for quantitative imaging of biological structures and phenomena. To conduct quantitative biological studies based on these new data, it is necessary to develop non-standard specific tools. This requires using a multi-disciplinary approach. We need biologists to define experiment protocols and interpret the results, but also physicists to model the sensors, computer scientists to develop algorithms and mathematicians to model the resulting information. These different expertises are combined within the Morpheme team. This generates a fecund frame for exchanging expertise, knowledge, leading to an optimal framework for the different tasks (imaging, image analysis, classification, modeling). We thus aim at providing adapted and robust tools required to describe, explain and model fundamental phenomena underlying the morphogenesis of cellular and supra-cellular biological structures. Combining experimental manipulations, in vivo imaging, image processing and computational modeling, we plan to provide methods for the quantitative analysis of the morphological changes that occur during development. This is of key importance as the morphology and topology of mesoscopic structures govern organ and cell function. Alterations in the genetic programs underlying cellular morphogenesis have been linked to a range of pathologies.
Biological questions we will focus on include:
-
what are the parameters and the factors controlling the establishment of ramified structures? (Are they really organize to ensure maximal coverage? How are genetic and physical constraints limiting their morphology?),
-
how are newly generated cells incorporated into reorganizing tissues during development? (is the relative position of cells governed by the lineage they belong to?)
Our goal is to characterize different populations or development conditions
based on the shape of cellular and supra-cellular structures, e.g. micro-vascular
networks, dendrite/axon networks, tissues from 2D, 2D+t, 3D or 3D+t images (obtained with confocal microscopy, video-microscopy, photon-microscopy or micro-tomography). We plan to extract shapes or quantitative parameters to characterize the morphometric properties of different samples. On the one hand, we will
propose numerical and biological models explaining the temporal evolution of the
sample, and on the other hand, we will statistically analyze shapes and complex
structures to identify relevant markers for classification purposes. This should
contribute to a better understanding of the development of normal tissues but
also to a characterization at the supra-cellular scale of different pathologies such
as Alzheimer, cancer, diabetes, or the Fragile X Syndrome.
In this multidisciplinary context, several challenges have to be faced. The
expertise of biologists concerning sample generation, as well as optimization of
experimental protocols and imaging conditions, is of course crucial. However,
the imaging protocols optimized for a qualitative analysis may be sub-optimal
for quantitative biology. Second, sample imaging is only a first step, as we need
to extract quantitative information. Achieving quantitative imaging remains an
open issue in biology, and requires close interactions between biologists, computer
scientists and applied mathematicians. On the one hand, experimental and imaging protocols should integrate constraints from the downstream computer-assisted
analysis, yielding to a trade-off between qualitative optimized and quantitative optimized protocols. On the other hand, computer analysis should integrate constraints specific to the biological problem, from acquisition to quantitative information extraction. There is therefore a need of specificity for embedding precise
biological information for a given task. Besides, a level of generality is also desirable for addressing data from different teams acquired with different protocols
and/or sensors.
The mathematical modeling of the physics of the acquisition system will yield
higher performance reconstruction/restoration algorithms in terms of accuracy.
Therefore, physicists and computer scientists have to work together. Quantitative
information extraction also has to deal with both the complexity of the structures of interest (e.g., very dense network, small structure detection in a volume,
multiscale behavior,
-
Imaging: this includes i) definition of the studied populations (experimental conditions) and preparation of samples, ii) definition of relevant quantitative characteristics and optimized acquisition protocol (staining, imaging,
) for the specific biological question, and iii) reconstruction/restoration of native data to improve the image readability and interpretation. -
Feature extraction: this consists in detecting and delineating the biological structures of interest from images. Embedding biological properties in the algorithms and models is a key issue. Two main challenges are the variability, both in shape and scale, of biological structures and the huge size of data sets. Following features along time will allow to address morphogenesis and structure development.
-
Classification/Interpretation: considering a database of images containing different populations, we can infer the parameters associated with a given model on each dataset from which the biological structure under study has been extracted. We plan to define classification schemes for characterizing the different populations based either on the model parameters, or on some specific metric between the extracted structures.
-
Modeling: two aspects will be considered. This first one consists in modeling biological phenomena such as axon growing or network topology in different contexts. One main advantage of our team is the possibility to use the image information for calibrating and/or validating the biological models. Calibration induces parameter inference as a main challenge. The second aspect consists in using a prior based on biological properties for extracting relevant information from images. Here again, combining biology and computer science expertise is a key point.