Contexte et atouts du poste
The PhD candidate will be hosted within the CITI laboratory, a joint laboratory between INRIA, INSA-Lyon and the University of Lyon, based in the metropole of Lyon in France.
The candidate will work within the MARACAS INRIA team in collaboration with the Institute for Mathematics and Scientific Computing, University of Graz, Austria.
The funding for this project will be obtained from the EEA Doctoral School within INSA-Lyon. As such, final approval of a candidate is required from the EEA after an interview.
This PhD project will be under the primary supervision of Prof. Chantal Muller (INSA-Lyon) and Dr. Malcolm Egan (INRIA) with additional supervision by Dr.
Bao Tang (Univ. Graz).
Scientific Background :
It is now common for biological systems to be viewed as information processing systems; that is, these systems are able to observe their environment via mechanisms such as chemosensing and control their internal state via biochemical regulatory networks.
Communication forms an additional aspect of such biochemical information processing systems, exemplified by quorum sensing in bacteria 8 .
In these biochemical systems, communication does not exploit electromagnetic signals common in networks designed for human-human or machine-machine communications.
Instead, communication is based on the exchange of information-carrying chemical species, known as molecular communication.
The idea of molecular communication has been present in areas such as cell-cell communications since the early days of systems biology.
However, the systematic design and analysis of molecular communication systems is still an emerging field beginning in 2005 9 .
The framework of molecular communications is expected to play an important role in the design of targeted drug delivery, in vivo sensing systems in biological environments (e.
g., in 4-7 ), and also in distributed spectroscopy for biological assays 1,11 . Indeed, a basic challenge in molecular biology is to measure small quantities of chemical species in order to ascertain how the state of the system evolves over time.
Using methods such as Raman spectroscopy or atomic force microscopy, it is in principle possible to make such measurements.
However, for in situ observations, specific conditions on the species of molecules being observed and the container must be met.
One approach to relax the conditions for in situ measurements is to exploit distributed spectroscopy on a lab-on-a-chip by using molecular communication which utilises microfluidic channels -to perform the measurements under simpler conditions, as proposed in our recent work in 1 .
As such, molecular communications provides key tools to significantly expand the ability to examine molecular level dynamics of biological systems.
Thesis Objectives :
A fundamental problem in molecular communications is how to encode a message into a quantity of a chemical species and, after passing through a fluid medium via reaction and diffusion, detect at the receiver which message was transmitted.
Recently, we have developed a new methodology, known as equilibrium signaling, to address this problem by exploiting equilibrium behaviour of reaction-diffusion systems modelled both by the reaction-diffusion master equation 3 and general Langevin diffusion models 2 .
Our approach is highly robust to variations in the environment (e.g., presence of obstacles, unknown diffusion coefficients).
Our methodology is also relevant for the design of distributed spectroscopy on lab-on-a-chip devices 1 .
Nevertheless, there remain some important issues to address in order to expand the utility of our methodology. Tackling the following issues will form the main objectives of the thesis :
1) A key assumption in our existing work 1-3 is that molecules do not degrade. The first objective in this thesis is to extend the methods in 1-3 to account for such degradation.
2) The design of the signaling strategies relies in 1-3 on a Gaussian approximation for the quantity of molecules observed by a receiver.
For simple reaction-diffusion systems, such approximations are well understood 12 ; however, for spatially inhomogeneous reaction rates and diffusion coefficients much less is known.
The second objective of the thesis is therefore to justify the Gaussian approximation, either via new central limit theorems or statistical model verification (as in 3 ).
3) In 1 , molecular communication was utilised in order to develop distributed spectroscopy on lab-on-a-chip devices. The third objective of the thesis is to dramatically expand the scope of our existing methods by incorporating degradation of molecules (via the results of objective 1) and account for device-specific constraints such as sampling rates, chemical properties of information-carrying molecules, and requirements of spectroscopy devices (e.
g., substrates necessary for atomic force microscopy).
1 Bayram Akdeniz and Malcolm Egan , Molecular Communication for Equilibrium State Estimation in Biochemical Processes on a Lab-on-a-Chip, accepted for publication in IEEE Transactions on NanoBioscience, (2021).
2 Malcolm Egan , Bayram Akdeniz and Bao Quoc Tang, Equilibrium signaling in spatially inhomogeneous diffusion and external forces, accepted for publication in IEEE Transactions on Molecular, Biological and Multi-Scale Communications, (2021)
3 Bayram Akdeniz, Malcolm Egan and Bao Quoc Tang, Equilibrium signaling : molecular communication robust to geometry uncertainties, accepted for publication in IEEE Transactions on Communications, (2020)
4 Akdeniz, Bayram Cevdet, and Malcolm Egan . "A Reactive Signaling Approach to Ensure Coexistence Between Molecular Communication and External Biochemical Systems.
IEEE Transactions on Molecular, Biological and Multi-Scale Communications 5.3 (2019) : 247-250.
5 Malcolm Egan , Loscri, V., Duong, T. Q., & Di Renzo, M. (2018). Strategies for coexistence in molecular communication.
IEEE transactions on nanobioscience, 18(1), 51-60.
6 Malcolm Egan , Trang C. Mai, Trung Q. Duong and Marco Di Renzo, Coexistence in Molecular Communications, Nano Communication Networks, vol. 16, pp. 37-44, (2018).
7 Trang C. Mai, Malcolm Egan , Trung Q. Duong and Marco Di Renzo, Event detection in molecular communication networks with anomalous diffusion, IEEE Communication Letters, vol.
21, no. 6, pp. 1249-1252, (2017).
8 M. Miller, B. Bassler. Quorum sensing in bacteria. Annual Reviews in Microbiology 55 (2001) pp. 2703-2738.
9 S. Hiyama et al. Molecular communication. Proc. NSTI Nanotechnology Conference (2005).
10 W. Pearman, M. Lawrence-Snyder, S. Angel, and A. Decho, Surface- enhanced Raman spectroscopy for in situ measurements of signaling molecules (autoinducers) relevant to bacteria quorum sensing, Applied Spectroscopy, vol.
61, no. 12, pp. 1295 1300, 2007.
11 Akdeniz, Bayram Cevdet, and Malcolm Egan . "A Molecular Communication Scheme to Estimate the State of Biochemical Processes on a Lab-on-a-Chip.
Proceedings of the 1st ACM International Workshop on Nanoscale Computing, Communication, and Applications. 2020.
12 T. Kurtz, The relationship between stochastic and deterministic models for chemical reactions, The Journal of Chemical Physics, vol.
57, no. 7, pp. 2976 2978, 1972.
Main activities :
The main work in this thesis is to address the three thesis objectives detailed above. Both mathematical analysis of the long-term statistics of reaction-diffusion systems and computer simulation studies of their behavior in the context of molecular communications will be required.
The precise mix of these aspects will be tailored to the background and interests of the candidate.
Languages : The working language for this project will be in English.