The University of Lausanne is a higher teaching and research institution composed of seven faculties with approximately 17,100 students and about 4,400 research, teaching and technical staff. The department of biomedical sciences is located in the city center close to the university hospital. This department hosts 15 research groups and nearly 120 collaborators in three distinct buildings.
The laboratory of cell-penetrating peptide biology is directed by Prof. Christian Widmann and is currently made up of 2 PhD students (eventually 4), 2 post-doctoral fellows and one technician (?url=https%3A%2F%2Fwp.unil.ch%2Fwidmannlab%2F172-2%2F&module=jobs&id=2431373" target="_blank" rel="nofollow">?url=https%3A%2F%2Fwp.unil.ch%2Fwidmannlab%2F172-2%2F&module=jobs&id=2431373" target="_blank" rel="nofollow">https://wp.unil.ch/widmannlab/172-2/). This laboratory studies the uptake mechanisms of cell-penetrating peptides (CPPs) and physiological proteins bearing CPP sequences such as homeoproteins (?url=https%3A%2F%2Fwp.unil.ch%2Fwidmannlab%2Fresearch%2F&module=jobs&id=2431373" target="_blank" rel="nofollow">?url=https%3A%2F%2Fwp.unil.ch%2Fwidmannlab%2Fresearch%2F&module=jobs&id=2431373" target="_blank" rel="nofollow">https://wp.unil.ch/widmannlab/research/). CPPs allow the intracellular delivery of cargo molecules that are hooked to them. They are used in biology and medicine for therapeutic or research purposes. CPPs are taken up by cells by direct translocation across the plasma membrane and by endocytosis, the two processes occurring concomitantly. CPPs can be found in anti-cancer and anti-microbial peptides but also in important signaling proteins such as homeoproteins. Despite their potential practical applications, the mechanisms of CPP entry inside cells are ill-defined and even controversial. The current focus of our laboratory is to characterize the mechanism of CPP cell entry via direct translocation or via endocytosis and how they escape endosomes when they use this later entry route. We also investigate how physiological molecules that naturally bear cell-penetrating sequences, such as homeoproteins, enter cells.
Please consult this movie (?url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv=vxLuPvS7yx4&module=jobs&id=2431373" target="_blank" rel="nofollow">?url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv=vxLuPvS7yx4&module=jobs&id=2431373" target="_blank" rel="nofollow">https://www.youtube.com/watch?v=vxLuPvS7yx4) that summarizes our recent findings on CPP cellular uptake.
Endocytosis is a major entry route used by cells to take up a variety of extracellular substances. The endocytosed material transits from early endosomes to late endosomes/lysosomes where they are degraded or recycled. Substances that are endocytosed through the classical pathway follow an endocytic maturation pathway towards Lamp1-positive lysosomes that is characterized molecularly by the presence of Rab5 on early endosomes and Rab7 on late endosomes/lysosomes. We have recently discovered a second endosomal pathway by studying how CPPs are taken up by cells. We have determined that progression along this endocytic pathway requires the Rab14 protein but not Rab5 and Rab7. We have also figured out that this endocytic route is taken by other, physiological, cationic cargos such as polyamines or homeodomains and that the LAMP1-positive compartment these cargos end in are not acidic, in contrast to what is seen in the classical endolysosomal pathway. The successful candidates will work on the recently identified Rab14-dependent pathway to characterize at the molecular level how it operates.
The successful applicant will have a master in cell biology, biochemistry or a related biological discipline. Required qualifications include prior knowledge on CPPs and endocytosis, creativity, the capacity to maintain excellent documentation of their work, to collaborate proficiently, and to communicate effectively with colleagues.
Two PhD positions to work on the Rab14 endocytic pathway in a dynamic and friendly research group. Investigation tools will include state-of-the-art biochemical, cellular and imaging techniques, as well as genetic manipulation based on the CrispR/Cas9 technology
Contact and Address
Prof. Christian Widmann, Departement of Biomedical Sciences, Bugnon 7, 1005 Lausanne, Switzerland
In your application, provide:
CV (one page max)
Names, emails and addresses of 2-3 reference persons
Letter of intent (one page max). Your past experience can be succinctly described but I am more interested in why you want to join my laboratory, what you want to investigate in my research group and how you would like to achieve this. Also detail why you think you are a good candidate for these PhD positions.
Important note: applications that do not strictly abide to the above instructions will be automatically discarded