Postdoc and PhD/Postdoc (mathematical modeling) in two EU consortia
Two positions, one 3-year postdoc (EU consortium anTBiotic) and one 3-year postdoc or PhD student (JPI-AMR consortium Collateral Damage) position, are available immediately in the Systems Pharmacology group of Dr. Pia Abel zur Wiesch. The position is affiliated with the Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership Molecular Medicine and is located at the University of Tromsø, Norway. While the primary location is in Tromsø, the candidates have the option to visit international collaborators in industry and leading universities.
About the group
The Systems-Pharmacology group is headed by Dr. Abel zur Wiesch, Tenure Track Associate Professor at UiT, NCMM Young Associate Investigator and Visiting Assistant Professor at Yale School of Public Health. The aim of our work is to improve therapy in infectious diseases by using mathematical models to predict how much drug a patient should receive and how long and how often the patient should be treated. Our mathematical models describe both the intracellular reaction kinetics of drug-target binding as well as growth and death of populations of bacterial or cancer cells (Abel zur Wiesch & al., Science Transl. Med. 2015, Abel zur Wiesch et al., PLOS Computational Biology). We collaborate closely with experimentalists and clinicians. Two examples of on-going projects are:
Tuberculosis (TB) today rivals HIV/AIDS as the leading cause of death from infectious diseases. The number of TB patients has never been higher and the growing proportion of drug-resistant TB is threatening control strategies both in the developing and developed world, Eastern Europe being a particularly worrying point in case.
The anTBiotic consortium aims to fuel the long-term TB clinical pipeline while immediately offering new options to clinicians when confronted with multidrug-resistant (MDR)-TB.
More specifically, the proposed studies aim to:
- Establish the proof of concept of anti-TB efficacy in humans of a pioneering, first-in-class, low-dose GSK oxaborole clinical drug candidate;
- Identify a combination of β-lactam antibiotics suitable for the treatment of MDR TB orally or as a once daily intravenous or intramuscular application; and
- Incorporate the best β-lactam combination into an explorative salvage regimen for untreatable patients with extensively drug-resistant TB.
The anti-TB activity in humans will be established in a two-week EBA clinical studies that combine established (CFU, TTP) and new clinical markers (biomarkers, PET/CT).
These datasets will help ascertain anti-TB efficacy in humans and generate confidence on their validity in longer-term drug combination trials. A variety of modelling approaches to predict optimal dosing will be used.
Finally, we intend to use at least one of these novel anti-TB entities as part of a pioneering, non-controlled clinical trial in highly drug resistant subjects in Europe and South Africa. This final clinical intervention will hopefully be of immediate benefit to drug-resistant patients in the EU and elsewhere in addition to generating a strong precedent for further adoption worldwide.
Urgent action is required to stem the “apocalyptic” spread of antimicrobial resistance (AMR). However, because the pace of novel drug development lags behind the evolution of novel AMR determinants, new strategies of containment are required. In this multidisciplinary project we develop a resistance-reversal strategy based on the concept of collateral sensitivity (CS). CS between a pair of antibiotics occurs when a mutation causing resistance to one antibiotic potentiates susceptibility to another. By exploiting CS relationships through sequential drug application, resistant strains can be specifically targeted which will reduce their frequencies in the community and slow their transmission. The broad aim in this project is to realize the unique promise of CS-informed therapies. To do so, our work packages integrate theoretical biology, evolutionary and molecular microbiology, and in vivo modelling with a specific focus on arresting the transmission of resistant Escherichia coli and Streptococcus pneumoniae.
Combining theory and experiments, we will: 1) test the generality of CS across hundreds of clinical strains of E. coli, and S. pneumoniae; 2) quantify how horizontal transmission of antimicrobial resistance determinants modify CS-networks; 3) identify the underlying molecular mechanisms of CS; and 4) determine the conditions under which CS mediated reversals of resistance occur in vivo.
The expected outcomes of the project are to provide pre-clinical recommendations for therapy to reduce the emergence and transmission of these two globally important bacterial pathogens and to provide a framework to develop CS-based strategies for other bacterial threats.
These two projects will combine mathematical modelling with the analysis of clinical and experimental data. The Systems Pharmacology group has documented expertise in all of these areas (Abel zur Wiesch & al., Science Transl. Medicine 2015, Abel zur Wiesch & al., Lancet Infectious Diseases 2011, Abel, Abel zur Wiesch & al., Nature Methods 2015), and we collaborate with leaders in the field of drug discovery and resistance evolution. The projects therefore offer a unique opportunity to get experience in a wide range of interesting research topics.
We seek candidates that appreciate working in an international and interactive environment, are highly enthusiastic about basic research with medical applicability, motivated and willing to integrate in a young team of researchers. You should have solid programming skills and a strong quantitative background and be passionate about applying your skills to biological and medical questions. A strong interest in Public Health, Pharmacology, Infectious Diseases, Biochemistry and/or Mathematical Biology is desirable. Previous experience with mathematical modeling and/or analysis of large datasets is an advantage. Good command of English and scientific writing skills are required. Applicants must hold a Master´s degree (or equivalent) for the PhD position and a doctorate equivalent to a Norwegian PhD for the postdoc position.
The successful candidate will work collaboratively with other faculty, scientists, and students in a dynamic and multi-disciplinary environment. We offer the unique opportunity of being embedded in several scientific environments at the UiT in Tromsø and the Centre for Molecular Medicine Norway (NCMM) in Oslo as well as our collaboration partners. We strongly encourage career development beyond authorship of research manuscripts arising from this work. We will help the successful candidate in developing their own interests and also encourage attending international conferences and visiting collaborators. UiT is a family friendly work environment and offers very attractive and internationally competitive benefits including pension arrangements, healthcare and other welfare benefits.
How to apply
The application deadline is November 20 and must be submitted in English. The following documents are required:
- 1-2 page cover letter explaining your motivation and research interests
- CV containing an overview of education, supervised professional training and professional work
- A complete list of publications
- Copies of diploma and transcript from completed degree(s) (translated to English or a Scandinavian language; certified copies must only be provided upon request)
- Name and address of 2-3 referees
- Documentation of English language proficiency may be required upon request
Please upload all your supplementary documents as one file
For more information, please visit our webpage.
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