Plasmodium falciparum growth in vitro and in vivo in humanised mice: implications for the design and evaluation of biological medicines
Dr A Nacer
Dr S Diebold
Prof J Rayner
No more applications being accepted
Funded PhD Project (European/UK Students Only)
A 3-year full-time PhD studentship is available at the Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), in collaboration with the Cambridge Institute for Medical Research (CIMR), University of Cambridge. The studentship is anticipated to commence in Autumn 2020.
Project description Plasmodium falciparum is the deadliest of the five species of Plasmodium, unicellular eukaryotic parasites, that cause malaria in humans. Despite intensive efforts and some success in reducing global malaria mortality rates over the last decade, there are still more than 200 million cases and nearly 0.5 million deaths from malaria each year, and control is challenged by drug resistance and the lack of an effective vaccine.
The ability to culture P. falciparum in vitro in human red blood cells underpins most of our current knowledge of parasite growth and metabolism, and has been pivotal to the development and testing of vaccines and drugs. However, we know that parasites change when they are adapted to culture conditions, and how good a model in vitro culture is for the growth of parasites in vivo is not known. These differences could impact the development of new therapies to reduce parasite burden and as a result severe malaria disease. For example, the ability of parasites to invade erythrocytes is of particular interest as a therapeutic target, because it is absolutely required for parasite growth and the blood stages of the life cycle cause all the clinical symptoms of malaria. Monoclonal antibodies or vaccines targeting either parasite or host proteins involved in invasion of erythrocytes have the potential to radically reduce parasite burden and therefore pathology, but whether in vitro culture systems serve as the best model to test such therapies is not clear.
We are interested in understanding how Plasmodium falciparum parasites differ between in vitro culture conditions and growth in vivo in the absence or presence of a human immune system. The PhD project will use next-generation sequencing to investigate the difference between in vivo and in vitro parasite transcription profiles using immunodeficient mice with or without a human immune system. Humanised mice provide a unique opportunity to explore whether targets identified in vitro are also functional in vivo as they are the only small animal model available for infection with this human-restricted pathogen. The project will require cell biology and molecular techniques including parasite culture, stem cell isolation and expansion, RNAseq, qPCR, flow cytometry, and immunoassays.
Candidates with an interest in genetics, host-pathogen interactions, or immunology are encouraged to apply, although experience in these areas is not necessary.
The successful applicant will be supervised by Drs. Adéla Nacer ([Email Address Removed]) and Sandra Diebold ([Email Address Removed]) at NIBSC, and Prof. Julian Rayner ([Email Address Removed]) at CIMR, University of Cambridge.
In addition to meeting all the academic, security and residency requirements, you will have:
• an academic background in molecular or cellular biology, parasitology, immunology or a relevant field
• a demonstrated aptitude in a laboratory setting and motivation to undertake research
• a demonstrated interest in the field of study and ability to work accurately and precisely
• demonstrate excellent oral and written communication, and IT skills
• a previous experience in one or more of the key interest areas as an advantage
• some theoretical knowledge of malaria parasites and antigenic variation
The student will be based at NIBSC but will also spend time at CIMR for training and laboratory work, in keeping with the residency requirements of the University of Cambridge. The successful applicant will be registered as a postgraduate student with the Cambridge Institute for Medical Research (CIMR) at the University of Cambridge and will therefore need to meet all University of Cambridge post-graduate admissions requirements.
Qualification requirements for University of Cambridge
Minimum entry requirements area 2:1 honours degree (or international equivalent) in a relevant subject. For international degrees please check eligibility at:
English language requirements Applicants whose first language is not English must fulfil the minimum requirements of an IELTS or TOEFL. An IELTS score of 7.0 with a minimum of 7.0 for listening, writing, and speaking and a of 6.5 for reading is required. Please visit https://www.graduate.study.cam.ac.uk/international/competence-english/what-tests-are-accepted for further details of the English competency assessments accepted by the University of Cambridge.
Visas and immigration
Applications are open to UK and EU students only, with demonstration of a right to reside in the UK.
To apply For further details of the project, essential requirements for study and details how to apply, see https://www.nibsc.org/about_us/careers_and_vacancies/phd_studentships.aspx?
Applications close 5:00pm (UK time), Friday 27 March 2020.
Send (i) your CV including the name and contact details of two academic referees and (ii) a personal statement of no more than 1000 words explaining your interest in this project and aspirations for undertaking a PhD to [Email Address Removed] by 17:00 GMT on Friday 27 March 2020. Please ensure the studentship reference number (PhD_BAC_NIBSC) is included in the subject line of the email and your personal statement.
The PhD is fully-funded by a NIBSC PhD studentship of 3 years that is open to UK and EU citizens only and includes the payment of tuition fees for the University of Cambridge and a stipend of £18,500 p.a.