Description of the thesis topic

Volatile Organic compounds analysis for Rapid Testing of Emerging respiratory infection using EXhaled breath

The analysis of volatile organic compounds (VOCs) in human breath holds valuable clinical potential and has been the subject of many breath research studies. The exhaled VOCs directly reflect human metabolism and therefore, they can indicate the pathophysiological status of the organism and further serve as potential biomarkers. Hence, we proposed developing a fast and non-invasive methodology, based on the chemical characterization of VOCs present in the exhaled breath. VOCs can be measured by means of online mass spectrometers and be used as specific markers, or metabolites, related to an infection. Within this Ph.D. work, in-vitro and in-vivo clinical studies will be performed to identify metabolites allowing the identification of viruses and bacteria infection including influenza viruses, SARS-CoV-2, and Legionella pneumophila.

To do so the Ph.D. candidate will be focused on
(i) the development of the VOCs emission of cellular cultures that will be infected with bacteria and viruses (Task 1.3) during the first 12 months of his work;
(ii) VOC analysis by Vocus-PTR during the clinical trial (Tasks 2.2 and 2.3). More specifically the Ph.D. candidate will be in charge of the instrument Vocus-PTR, and will be helping to collect the breath during the clinical trial. This will be part of the first and second year of his Ph.D.

Then, the main work done by the candidate
(iii) will be to perform the in-vitro experiments, especially on axenic and cell culture for Legionella. She/he will be in charge to design the experimental procedure, to collect the data (Task 3.1). This work will be done in collaboration with the second PhD from VirPath team who will be trained in viral culture;
(iv) In addition, the candidate will be responsible for analyzing the VOCs data collected during the different tasks and directly interacting with the biostatisticians to develop an analysis methodology to identify biomarkers and VOC profile (WP.4). Comparison of the chemical composition obtained during the in-vitro vs in-vivo experiments will be also attempted to evaluate the feasibility of identifying key VOC markers from simplified cellular systems.

Work Context

Human interaction and international trade have accelerated the spread of invasive species and viruses, which have severe consequences economically, environmentally, and ecologically. The COVID-19 pandemic, which circulated in 206 countries and resulted in millions of deaths, is a prominent example of how fragile we are to pathogens and how widely and rapidly they spread due to trade and travel. This ongoing health crisis also highlights our major limitations in the current medical testing methods, which are limited to a few hundred tests/1Mpop/day and remain extremely slow in an outbreak situation. Furthermore, it shows that viral transmission, especially through airborne aerosol routes, is not well understood, due to the lack of techniques capable of detecting airborne viruses. With the increase in human mobility, viral and/or bacterial pandemics are expected to increasingly threaten our survival. To contain them, we need to accelerate medical testing and increase their accessibility to a wider population. In summary, there is a clear need to develop the capabilities of detecting pathogens and viruses at the early stages of infection, to effectively manage their health impacts.

One promising approach, that was tested during the COVID-19 pandemic is analyzing exhaled breath, which contains volatile organic compounds (VOCs). Detecting specific VOCs linked to specific diseases or metabolic processes could significantly enhance disease diagnosis, offering a rapid, non-invasive, and cost-effective alternative to conventional diagnostic methods. The aim of this Ph.D. work would be to develop a methodology based on newly designed proton transfer reaction and time-of-flight mass spectrometry (Vocus-PTR) which represents the gold standard method to analyze VOCs in exhaled breath to identify metabolites allowing the identification of viruses and bacteria infection including influenza viruses, SARS-CoV-2, and Legionella pneumophila.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Constraints and risks

The interdisciplinary work will take place at the interface between two research institutes (CIRI and IRCELYON) and will promote collaboration and interaction within the VORTEX project. The candidate will acquire a dual competence in biology, including the physicochemical aspects, microbiology, and pathogen-host cell interactions, in analytical chemistry (mass spectrometry) and statistical analysis (clustering analysis). She/he will be trained for different models of culture cell infection using A549, THP1 cells, and in vitro 3D upper airway and alveolar epithelium models.