PhD Student

Last application date
Aug 15, 2021 00:00
Department
DI02 - Department of Pharmacology, Toxicology and Biochemistry
Contract
Limited duration
Degree
You have obtained a master degree in Veterinary Medicine or in Medicine.
Occupancy rate
100%
Vacancy type
Research staff

Job description

At the Faculty of Veterinary Medicine (n° 1 University in the Global Ranking of academic subjects, Veterinary Sciences), we are looking for a highly motivated researcher to join the Laboratory of Pharmacology and Toxicology. The aim is to pursue a PhD degree on the STOP_SEPSIS project: investigation into a new concept of sepsis, the greatest unmet medical need of our times.

As sepsis hits 49 million people per year, killing 11 million of them, it is the most urgent unmet medical condition of today. In a mouse model of sepsis, we have found that lethality is linked to loss of function of the transcription factor PPARa in hepatocytes. PPARa is the coordinator of fatty acid beta oxidation and ketogenesis, i.e. the transformation of free fatty acids (FFAs) into acetyl-CoA and ketone bodies. In sepsis, FFAs are massively released from fat and so they accumulate in tissues because they are not transformed to ketone bodies. These latter are essential to prevent coma and heart failure. RNA sequencing of livers from septic mice, revealed that the decline in PPARa mRNA is strongly predicted to depend on a progressive failure of HNF4a, a key transcriptional regulator of hepatocyte differentiation. So, in sepsis, the loss of HNF4a function leads to de-differentiation of hepatocytes, which is reflected in decreased expression of many other genes, i.e. cytochrome p450 (CYP450) coding genes. The cause of the HNF4a failure and de-differentiation of the liver and the role it plays in the progression of sepsis form the basis of this project.

Your specific research aims:
You will develop a pig sepsis model and confirm that the most important findings about the HNF4α failure, liver de-differentiation, blood FFA rise, CYP450 genes decline and other relevant findings in mouse sepsis, are equally occurring and relevant in pigs. Previous research at the Faculty of Veterinary Medicine has shown that the conventional pig(let) is a highly relevant preclinical animal model for translational drug research for humans, including children. See also: https://www.ugent.be/di/ftb/en/research/lab-pharmacology-toxicology. The pig model will also be applied to confirm that the optimal therapy, as developed in mice, is relevant in pig sepsis.

Utilization of project results is envisaged as well in the pharma/biotech as in agrifood industry. The long-term utilization objective is to translate the knowledge from this project’s results into marketable new product developments. Such products could consist of feed additives, food supplements, nutraceuticals, metabolic health markers, OTC pharmaceutical products or drugs. This will be studied in cooperation with the business development center DiscoverE (dr. Dominic De Groote) and the Industrial Research fund platform Cross-Health dealing with medicine for man and animal (dr. Laetitia Cicchelero).

Job profile

  • You have a strong motivation to conduct research, can work independent, but can also function as part of a multidisciplinary team.
  • You are looking forward to work in a multidisciplinary team, together with fellow PhD students performing similar research in mice (promoters prof. Claude Libert (project coordinator) and prof. Karolien De Bosscher of UGent and VIB), a post-doctoral follow, and study nurse at UZGent (promoter prof. Jan De Waele, UZGent, Intensive Care).
  • You should be willing to conduct animal experiments with pigs (being certified to conduct animal experiments in the EU is recommended).
  • You are willing to learn to write academic papers and have communication skills to present your results in English
  • A thorough knowledge of the Dutch or English language is mandatory.

How to apply

Please send a letter of motivation in Dutch or English, CV and copy of your diploma to prof. dr. Siska Croubels (siska.croubels@ugent.be).