The project aims to investigate epigenetic influence of the memory function of epithelial cells (organoid) in ulcerative colitis (UC), one of the two main entities of inflammatory bowel disease (IBD). A well-functional epithelial layer is of paramount importance for segregation between luminal content of dietary antigens or microbiota and the host, and thereby maintenance of gut homeostasis. This gut barrier is constantly being challenged, and a leaky barrier has serious consequences for infection and inflammation and is involved in the pathogenesis of a wide range of inflammatory disorders, including UC.
The Department of Gastroenterology, Herlev Hospital, is an East Danish IBD Center (with a cohort of close to 4,000 patients). UC constitutes approximately 2/3 of the entire IBD population, and approximately 0.6% of all Danes have IBD. With this project, we want to expand knowledge whether certain medications used for the management of IBD may change the natural history of UC, such as risk for relapses as well as treatment response over much longer time spans than their pharmaceutical lifetime in the body. Classical glucocorticoids are generally used in newly diagnosed patients with UC to control acute, flaring inflammation before other medications potentially are prescribed. However, glucocorticoids may change the response patterns of gut cells long time after an exposure by yet unknown mechanisms. Such phenomena are contingent on the issue that IBD-related cells carry a memory of previous events through epigenetic states such as DNA methylation and DNA accessibility, or chromatin modifications. However, at present this process is enigmatic. Further elucidation is imperative to predict the efficacy of drugs for a given patient over time and at repeated exposures. Revealing epigenetic modifications in UC and their relation to treatment responses may lead to better disease control, including more effective and rational use of therapeutic options, as well as prevention of flares and progression.
We plan to assess how glucocorticoids affect the epigenetic state of epithelial cells, including its influence on clinical disease outcomes, and the relative effects on accessible chromatin, methylation and active or repressive histone marks, as well as active transcription using multivariate statistical methods. Importantly, we already hold extensive experience with ATAC-seq, genome-wide methyl-seq, ChIP-seq, CAGE-seq and traditional RNA-seq using organoid systems.
Job accountabilities: As a Postdoctoral Fellow, you will be responsible for collecting biological test material from our large Endoscopy Unit (performing around 9.000 lower endoscopies yearly) and be in charge of long-term culturing of primary intestinal epithelial cells as organoids at the hospital department’s research facility. Molecular biology analyzes will be performed in close collaboration with The Kim B. Jensen Laboratory, and bioinformatics with the Albin Sandelin facility of Computational and RNA Biology, both located at BRIC nearby. You will additionally be responsible for data processing and compilation of results for subsequent scientific publications in acknowledged scientific journals. These tasks will be performed in close cooperation with the research team as well as dedicated biotechnicians, and in a simultaneous academic interaction with clinicians and basic scientists. As you become a central part of the project team, it is critical that you are a well-structured person with a good drive who is committed to join a dynamic team with the other research group members, and that you have a strong interest in conducting collaborative research on the topic mentioned.
Job requirements: The vacant postdoc position scheduled for 2 – 4 years is available for an enthusiastic and highly motivated researcher with a master’s degree as well as a PhD or equivalent doctorate within previous five years in immunology, molecular biology, or a related discipline. A strong publication record and training (i.e., 1-2 years of experience in working with stem cells as well as demonstrated expertise in the use of cell culturing, studies of cell metabolism, biochemistry, and molecular biology) is required for further consideration. Thus, it is crucial that you have a well-founded biological insight; have flair and desire to collaborate in the field of bioinformatics and statistics, and that you are fluent in both oral and written English. Moreover, you must be able to work independently in the team of physicians and researchers.
Job Location: The Research Lab, Department of Gastroenterology, Herlev Hospital and the nearby Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Denmark. Thus, Herlev Hospital is a tertiary referral university hospital of the Copenhagen Capital Region. Moreover, BRIC which was established in 2003 by the Danish Ministry of Science, Technology and Innovation to form an elite center in biomedical research with the aims to perform interdisciplinary, cutting-edge research and to promote exchange of ideas within the national and international biotech research community.
Salary: Salary will be at or above guidelines set by the Danish salary agreement for public service employees.
Application: Candidates should include an updated CV with uniqueness of bibliometric data; complete information for three references, and a motivation letter describing their past research experience, career goals and potential future research interests. Applicants should send letter of application and resume to: Professor Ole Haagen Nielsen, MD, DMSc, Department of Gastroenterology, Herlev Hospital, Copenhagen, Denmark (firstname.lastname@example.org) before March 23rd, 2020.