Download Projects

PhD and postdoctoral projects (Group of Mathematical Epidemiology)
Project 1. Modeling virus-host interaction during viral infection of a single cells
Supervisors: Andrei Korobeinikov (CRM), and Juana Diez, Jordi Garcia Ojalvo and Andreas
Meyerhans (Department of Experimental and Health Sciences, Universitat Pompeu Fabra)
Viruses are intracellular parasites, which need cellular components to replicate. While many
individual interactions between an infecting virus and cellular host factors have been
identified, their all-over complex interplay in terms of dynamics and outcomes are not well
understood. The aim of this project is to generate mathematical models, which enable
obtaining a quantitative understanding of the outcomes of virus – host factor interactions with
respect to virus production per an infected cell. This outcome will potentially allow to identify
the step in the virus life cycle, which has the biggest impact in virus expansion, and thus define
the best target for antiviral drug interventions (antiviral therapy). Another goal of this project
is motivated by the fact that multiple infections of a single cell can lead to reshuffling of viral
genomes with the concomitant production of recombinant viral progeny. In this project
mathematical modeling shall also be applied to answer fundamental questions about the
dynamics of variant generation under different single cell infection conditions.
Project 2. Dynamic properties of immune cell populations in response to viral infections
Supervisors: Andrei Korobeinikov (CRM), and Jordi Garcia Ojalvo and Andreas Meyerhans
(Department of Experimental and Health Sciences, Universitat Pompeu Fabra)
The adaptive immune response is a very efficient mechanism of the body defence again a
microbial infection, and the proliferation of lymphocytes, which follows an infection and
activation of the immune response, is its key component. Existing experimental methods allow
labeling cells using fluorescent dyes and then following the proliferation of these cells by dye
dilution with flow cytometry. However, the underlying dynamic properties and mechanisms of
the proliferation to a large extend remains a mystery and a major challenge for immunologists.
The aim of this project is to develop mathematical tools that enable reliable estimation of
fundamental proliferation parameters, such as proliferation rates, death rates and time to first
division, and relate those to different outcomes of real-life viral infections.
Project 3. Viral evolution and immune responses
Supervisors: Andrei Korobeinikov (CRM), and Jordi Garcia Ojalvo and Andreas Meyerhans
(Department of Experimental and Health Sciences, Universitat Pompeu Fabra)
Microbial mutation and evolution is probably the most significant single factor accountable for
emergence of pathogens and drug-resistant strains, and preventing the development of
effective drugs and vaccines. A particular question which this project shall address is about the
role of immune selection pressure generated via a number of mechanisms such as neutralizing
antibodies or cytotoxic T lymphocytes in natural selection and viral evolution. Another related
question is whether and how HIV variation is linked to the development of AIDS. Answering
these questions will allow us to better predict the long-term spread of drug resistance and CTLescape mutations, as well as the likely impact of vaccination. Accordingly, our goal is to
develop mathematical models of viral evolution which include immune response and antiviral
therapy and which enables us to address these question.
Project 4. Virus-induced modulation of cytokine signalling
Supervisors: Andrei Korobeinikov and Tomas Alarcone (CRM), Jordi Garcia Ojalvo (Department
of Experimental and Health Sciences, Universitat Pompeu Fabra) and Pablo Villoslada (IDIBAPS)
Cytokine signalling is one of the main effectors of the immune response in our bodies, and as
such it serves as the basis for a wide range of therapies against a variety of diseases, by either
activating or inhibiting the immune system. An important example of such a disease and a
therapy is the use of immune-suppressive drugs, which is used to fight autoimmune disorders
such as multiple sclerosis. A common treatment of multiple sclerosis is based on the cytokine
known as interferon beta, which activates among others the Jak/Stat pathway. The goal of this
project is to examine, by means of a combination of mathematical modelling and experimental
studies, how the presence of viral species, such as the Epstein-Barr virus, affects the response
of the Jak/Stat pathway to interferon beta, with the goal of shedding light on the large
variability observed in the efficacy of that therapy among multiple sclerosis patients.
Project 5. Optimizing vaccination scheduler for sexually transmitted diseases, and in
particular for human papillomavirus (HPV) 16 and 18 infection.
Supervisors: Andrei Korobeinikov and Tomas Alarcon (CRM), and Mireia Diaz Sanchis (Unit of
Infections and Cancer, Institut Català d' Oncologia, IDIBELL).
Recently, efficacious vaccines against HPV-16 and -18 were developed and vaccination started.
Taking into consideration vaccination costs, there are important questions regarding the
appropriate target population, as well as a vaccination scheduler for prophylactic vaccination
against HPV-16 and HPV-18. A purpose of this project is to answer these questions and to
assist in designing rational vaccination strategy. Our goal is to develop a hierarchy of
mathematical models of sexually transmitted diseases, with particular emphasis to human
papillomavirus (HPV), and study possible outcomes of different vaccination scenarios. At the
second stage of the project, using methods of the optimal control theory, we plan to develop
mathematical tools for designing optimal, in a certain sense, vaccination strategy for a variety
of practically relevant objectives. We believe that the expected results will be applicable to
prophylactic vaccination against other sexually transmitted infections.
Project 6. Modelling the dynamics of marine food webs under different type of perturbations
Supervisors: Andrei Korobeinikov and Tomas Alarcone (CRM), and Francesc Maynou (Institut
de Ciències del Mar, CSIC)
Ecological webs define complex interactions and dynamics among species inhabiting marine
ecosystem. Among ecological interactions, food interactions can be described by the so called
trophic web and constitute a complex energetic system. Understanding and quantifying the
dynamics of marine food webs is difficult because of nonlinearities in the system and
uncertainties in the observational data sets. Species change their behaviour mainly with
respect to source availability. For example its scarcity can lead to competition and migration
and necessarily to an alteration of food interactions. In turn these interactions can be affected
by the human exertion for example in marine ecosystems through fishing activity. To date the
response of the food web structure has been studied with respect to single perturbation
events, however many disturbances are continuous over time, and dynamic simulations of
single perturbation or catastrophic events are inappropriate. The aim of this project is to
develop mathematical tools to enable understanding the dynamics of marine complex systems
subject to environmental and human continuous perturbations.
Candidates’ specification
For a PhD position, we are happy to consider applications from suitably qualified candidates,
who either hold, or expect to get a good Master of Science degree in mathematics, physics, or
biology (in the latter case a substantial training in mathematics will be required). We expect
familiarity with numerical methods or principles of mathematical modelling. Knowledge of
biology is not essential, but would be a strong advantage.