PhD position on genetics and biology of Congenital Disorders of Glycosylation

Research into rare diseases to reveal fundamental biological pathways and to improve patient care

30 July 2020

Apply before 31 August 2020

At the Laboratory for Molecular Diagnosis at the Center for Human Genetics, KU Leuven, Belgium, we focus on the systematic search for novel types of Congenital Disorders of Glycosylation (CDG) and their subsequent characterisation. CDG are a group of rare inborn errors of metabolism that lead to a broad range of clinical presentations such as intellectual disability, skeletal abnormalities and epilepsy. Our work covers both the fundamental and translational realms of science by helping us to understand the function of poorly understood genes and proteins and simultaneously providing a diagnosis to affected patients using state-of-the-art technology such as whole genome sequencing (WGS). At the Structural and Functional Glycobiology Unit (UGSF, UMR 8576) at the University of Lille, France, the focus is on understanding the impact of vesicular trafficking, and of manganese and calcium ER/Golgi homeostasis, on the regulation of the glycosylation process.

The position is opened in the context of a joint project co-hosted by KU Leuven and the University of Lille. It is expected that the successful candidate will spend approximately 24 months in each centre during the course of their 4-year PhD programme.

The identification and diagnosis of patients with Congenital Disorders of Glycosylation (CDG) is hampered by an extremely variable presentation ranging from single organ failure to complex disease with neurodevelopmental anddysmorphic features. Compounding this, there are also a huge number of genetically distinct CDG (>150 in total), many with only a few known cases. CDG are caused by mutations that affect the formation, trafficking or processing of glycans, leading to the aberrant glycosylation of proteins, this also makes the biochemical mechanisms leading to disease difficult to understand. Our laboratory has, for more than 20 years, been at the forefront of the identification of novel CDG. This includes the most common CDG subtype caused by mutations in PMM2 (Matthijs et al. 1997), and subsequently others such as COG1-CDG (Foulquier et al. 2007), COG4-CDG (Reynders etal. 2009), COG8-CDG (Foulquier et al. 2007) and MAN1B1-CDG (Rymen etal. 2013). Most recently, our focus has been upon CDG affecting the function of the oligosaccharyltransferase (OST) complex (Blommaert et al.2019).

The aim of this project will be to characterise novel CDG that have recently been identified in our lab through the screening of undiagnosed CDG patients using whole genome sequencing (WGS). This will be carried out using a variety of molecular biology techniques for the investigation of these defects in primary dermal fibroblasts derived from affected patients, as well as mammalian and fungal cell models. A successful candidate will also be trained in the analysis of WGS data from‘unsolved’ patients, in the hope of achieving diagnoses. This will include the application of state-of-the-art bioinformatics tools. The functional studies, including cell-biological, glycobiological and enzymatic experiments will be carried out under the supervision of Dr. François Foulquier, at the University of Lille.


Profile

  • You have obtained a Master’s degree in Biomedical Sciences, Medicine, Pharmacy, Biochemistry, Bioengineering, Biology or a related field, with excellent results.
  • You have a passion for science and have the commitment and motivation to pursue completion of a doctorate over four years, divided between KU Leuven and the University of Lille.
  • You have excellent spoken and written English skills, and want to work in a truly international environment.
  • You have at least some prior training in the use of standard molecular biology techniques and cell culture, and/or in genetics and bio-informatics.
  • You must be equally capable of working in a group and pursuing independent research goals, as well as an excellent communicator

Offer

  • You will perform cutting edge research at the forefront of both fundamental and translational science in the context of CDG, a rapidly expanding group of disorders that are still poorly understood.
  • You will receive expert training in both biological and bioinformatic techniques required for the completion of the PhD program.
  • The multidisciplinary research team is at the interface of fundamental and clinical research, and the team members interact directly with clinicians, and is at the heart of a European research network on CDG and related disorders.
  • You will have the opportunity to travel and collaborate with several groups, both national and international, in addition to the 50% of this project which will be carried out at KU Leuven and University of Lille.
  • The PhD would begin 1st October 2020, but this is flexible in consultation with the supervisor.
  • The project will lead to a double doctoral degree, from KU Leuven as well as from University of Lille