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Postdoc in Genetic studies of extreme obesity in consanguineous Pakistani families

Novo Nordisk Foundation Center for Basic Metabolic Research
Faculty of Health and Medical Sciences
University of Copenhagen


The University of Copenhagen is seeking a highly motivated and talented postdoctoral fellow to commence October 1, 2021 at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), University of Copenhagen.

The postdoctoral fellowship is part of the Novo Nordisk Foundation Center for Basic Metabolic Research International Postdoctoral Program www.cbmr.ku.dk/postdocprogram.

About Us
The Novo Nordisk Foundation Center for Basic Metabolic Research’s vision is to strengthen interdisciplinary research that transforms our basic understanding of the mechanisms that underlie metabolic health and disease, and to accelerate this knowledge toward new prevention and treatment strategies. We were established in 2010 and in 2017, we moved into new laboratories, offices and meeting rooms in the Maersk Tower www.maersktower.ku.dk.

The Center has around 240 employees who work in an international, highly collaborative research environment across a range of biomedical disciplines. You can read more about us here: www.cbmr.ku.dk.

Our Research
In the molecular understanding of metabolic diseases, a major gap exists between basic genetic and microbiome discoveries and their impact on physiology and the potential for clinical translation. The Hansen Group in the Center aims to bridge this gap by connecting genomic discoveries and epidemiology with physiology and clinical application. To study the role of selected genetic variants in human metabolism, we perform physiology and intervention studies based on recruit-by-genotype principles.

We also investigate families and populations with extreme metabolic phenotypes and perform physiology and intervention studies.

Finally, we investigate targeted clinical management of carriers of selected high-impact variations in the human genome.

You can read more about the Hansen Group here:

https://cbmr.ku.dk/research/human-genomics-and-metagenomics-in-metabolism/hansen-group/

In the Hansen Group, we strive for an inclusive and social work environment where support and constructive feedback is offered within the group.

Job Description
With the project ‘Genetic studies of extreme obesity in consanguineous Pakistani families’, it is our ambition to perform whole genome sequencing (WGS) in 130 Pakistani families with one or more children with extreme obesity, and to identify and characterize novel obesity genes. This will generate new insights into the function of novel obesity genes and it will facilitate studies of obesity in other populations, with the perspective to improve our understanding of early stages of the development of obesity. The study will include 1) whole genome sequencing, 2) analysis of protein stability, 3) mapping obesity genes to cell types, and 4) analysis of selected loci using recessive models in other study populations.

This project will enable us to identify novel genetic variation associating with early onset obesity. We will elucidate the impact of the disease associated variants on the molecular level combining biophysical modelling of protein folding and stability with advanced sequence analyses to interpret variant effects. Furthermore, in-house initiatives to characterize open chromatin and cell type specific gene regulation will allow us to map the effect of the variants to the cellular and tissue level. Finally, we will examine whether the gene/genes associating with childhood obesity in Pakistani families might associate with obesity/BMI in other non-European populations, in Danish children with early onset obesity and in large populations based studies (i.e. UK biobank) applying recessive analytical models. The results will be used to propose and develop new approaches to diagnose, prevent and treat early onset obesity.

Your tasks would be:

1. Whole genome sequencing

In collaboration with the International Islamic University, we have collected 130 families with one or more children with severe early onset (before 5 years) obesity. All families are consanguineous and genomic DNA has been obtained from at least 3 family members (proband, mother and father). In total, we have DNA from more than 500 individuals. All families has consented to have WGS performed. Furthermore, it will be possible to re-contact families to do re-call Phenotype studies.

2. Analysis of protein stability

Together with Professor Kresten Lindorff-Larsen, Structural Biology and NMR Laboratory & Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, we will use computational methods to analyze and provide mechanistic hypotheses for identified variants in coding regions. Professor Kresten Lindorff-Larsen is PI and Torben Hansen co-PI on the PRISM (Protein Interactions and Stability in Medicine and Genomics) programme funded by the Novo Nordisk Foundation Challenge Programme.

3. Mapping obesity genes to cell types

We will capitalize on the recent CBMR flagship initiative SEGMENT – Single-cell Genomics to Map Diabetes and Obesity Heterogeneity. The single-cell omics platform at the Center has developed protocols for extraction of nuclei from frozen biopsies and can reliably isolate +10,000 nuclei/mg tissue from selected tissues for single-cell analyses. By combining chromatin accessibility with ChIP sequencing on a single cell level, you will also be able to reliably map enhancer-promoter regulation through the recently published “activity-by-contact” (ABC) model.

4. Analysis of selected loci using recessive models in other study populations

We have access to large population-based data on obesity in Denmark (n+100,000) and internationally (i.e. UK biobank). You will examine whether variations in the gene/genes associating with childhood obesity in Pakistani families might associate with obesity/BMI in other non-European populations, in Danish children with early onset obesity and in large populations based studies (i.e. UK biobank) applying recessive analytical models.

Profile
The fellowship is aimed at early career researchers with a basic science background or clinicians who aspire to a career in academic medicine. We are particularly interested in candidates who are familiar with integrative research approaches within the broad area of basic metabolic research with an application towards human pathophysiology.

Required qualifications:

  • PhD in Bioinformatics, Statistical Genetics, Biology, Biochemistry, Molecular Biology, Molecular Biomedicine, or related sciences
  • Excellent scientific track record in relation to career stage
  • Profound knowledge in bioinformatics and genetics
  • Knowledge in metabolic diseases, especially obesity
  • Experience with analysis of next generation sequence data and integration of multiple data layers
  • Excellent English communication skills, both written and oral
Eligibility
The CBMR International Postdoctoral Program is open for applicants that hold a PhD degree awarded from a university outside of Denmark. The PhD degree has to be obtained before October 1, 2021. The program is also open for applicants with a Danish PhD degree who can document at least 12 months full-time research experience from outside Denmark. You are not eligible to apply for the program if you have been employed in a postdoctoral position for more than one year at the University of Copenhagen prior to the commencement of the fellowship.

Terms of Employment
The employment as postdoc is a full time position for 3 years. Starting date is October 1, 2021.
Salary, pension and terms of employment will be in accordance with the agreement between the Danish Ministry of Finance and AC (Danish Confederation of Professional Associations). Depending on qualifications, a supplement may be negotiated.
Non-Danish and Danish applicants may be eligible for tax reductions, if they hold a PhD degree and have not lived in Denmark the last 10 years.

Questions
For further information about the position, please contact Professor Torben Hansen at torben.hansen@sund.ku.dk. Questions regarding the CBMR International Postdoctoral Program must be directed to cbmr@sund.ku.dk. For questions regarding the recruitment procedure, please contact HR at sund-hr-cbmr@sund.ku.dk.

The University of Copenhagen International Staff Mobility office offers support and assistance to all international researchers on all issues related to moving to and settling in Denmark. Read more at www.ism.ku.dk.

Application Procedure
Your online application must be submitted in English via the ‘Apply now’ link below. Furthermore, your application must include the following documents/attachments – all in PDF format:

  • Cover letter expressing the motivation and previous research experience of the applicant (max 1 page)
  • Curriculum vitae
  • Copy of the PhD degree certificate and the Master degree certificate. In case the PhD has not yet been completed, a written statement from the supervisor confirming it will be obtained before October 1, 2021 is acceptable.
  • List of publications
  • References (name and contact details of at least two references)
Application Deadline: April 19, 2021, 23.59pm CET

We reserve the right not to consider material received after the deadline, and not to consider applications that do not live up to the abovementioned requirements.

The Further Process
After the expiry of the deadline for applications, the authorized recruitment manager selects applicants for assessment on the advice of the hiring committee. All applicants are then immediately notified whether their application has been passed for assessment by an unbiased assessor. Once the assessment work has been completed, each applicant has the opportunity to comment on the part of the assessment that relates to the applicant him/herself.

You can read about the recruitment process at www.employment.ku.dk/faculty/recruitment-process.

The applicant will be assessed according to the Ministerial Order no. 242 of March 13, 2012 on the Appointment of Academic Staff at Universities.

The University of Copenhagen wishes to reflect the diversity of society and welcomes applications from all qualified candidates regardless of their personal background.

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