Karolinska Institutet (KI)

Doctoral (PhD) student position in ‘Macrophage epigenome alterations in atherosclerosis’

Karolinska Institutet (KI)

Huddinge, Sweden

The Department of Biosciences and Nutrition performs research and education in several areas of medical science including bioorganic chemistry, molecular endocrinology, cancer biology, functional genomics, systems biology, epigenetics, structural biochemistry, cellular virology, and nutrition. It offers an excellent international research and working environment, including around 250 scientists, students, administrative and technical personnel. The Department resides in the new biomedical research building Neo, aimed at being a creative and open environment that enables meetings, synergies, and exploration of areas of mutual interest across disciplines.

Do you want to contribute to top quality medical research?

To be a doctoral student means to devote oneself to a research project under supervision of experienced researchers and following an individual study plan. For a doctoral degree, the equivalent of four years of full-time doctoral education is required.

The research group
The position will be placed in the laboratory of Prof. Eckardt Treuter which conducts pre-clinical research at the crossroads between epigenomics, metabolism, inflammation and disease. Our research aims at better understanding how the epigenome controls metabolic and inflammatory pathways in the context of obesity, type 2 diabetes, fatty liver disease and atherosclerosis. Epigenetic alterations that trigger changes in epigenome activity and gene expression are fundamental reprogramming events that contribute to the development of these diseases. However, the underlying regulatory mechanisms, the critical components, and the causal relationship of these associations are currently poorly defined. With an emphasis on so-called coregulators we address these issues utilizing a multidisciplinary approach, including molecular biology, biochemistry, genomics and epigenomics approaches, genetically modified cell, tissue and mouse models, and collaborations with clinicians to study human material. We also develop proof-of-concept models for the therapeutic targeting of epigenome components, such as chromatin-modifying complexes and enhancers.

https://ki.se/en/bionut/epigenetic-mechanisms-underlying-metabolic-inflammatory-diseases-eckardt-treuter

The laboratory is placed in the Department of Biosciences and Nutrition at Karolinska’s South Campus, a creative and open environment.

The doctoral student project and the duties of the doctoral student
The project:
AIM: This PhD project will investigate the role of macrophage epigenome alterations in the progression of atherosclerosis. Focus will be on two interconnected epigenome components, i.e. (1) a fundamental corepressor complex containing G-protein pathway suppressor 2 (GPS2), and (2) selected pro-atherogenic (inflammatory, metabolic) enhancers that are controlled by the complex (reviewed in Treuter et al. FEBS letters 2017).

RATIONALE AND HYPOTHESIS: Circulating monocytes and monocyte-derived tissue macrophages control inflammation and cholesterol efflux, key processes involved in atherogenesis. Previous work of the laboratory (e.g. Jakobsson et al. Mol Cell 2009, Venteclef et al. Genes Dev 2010; Fan et al. Nat Med 2016, Huang et al., FASEB J 2019; Liang et al Nat Comm 2019) has revealed that both processes are in part controlled by the subunit GPS2, within distinct corepressor sub-complexes, in macrophages. Epidemiological evidence suggests that obesity and type 2 diabetes are risk factors for developing cardiovascular diseases. Since our work additionally revealed that the expression and function of GPS2 in monocytes/macrophages is altered in obesity and type 2 diabetes, there could be a causal link between these alterations and epigenome/enhancer activity in re-programming gene expression to drive atherogenesis.

SIGNIFICANCE: The project is expected to increase our understanding of the atherogenic macrophage epigenome and the epigenetic mechanisms, including ‘memory’, that link obesity/type 2 diabetes and cardiovascular disease/atherosclerosis. Thereby, the project may contribute to the development of epigenome-based therapeutic strategies that specifically target pro-atherogenic pathways in monocytes/macrophages.

Duties:
The PhD student will establish and manipulate human monocyte-derived macrophages in vitro to identify GPS2-dependent and -independent epigenome/enhancer alterations with an emphasis on relevance for atherogenic pathways in humans. This involves the application of latest CRISPR/Cas-9 techniques to modulate chromatin structure and activity, along with ChIP-seq, ATAC-seq, RNA-seq, ChIP-mass spectromentry and bioinformatics analysis. Ideally, the student will gain both wet and dry lab experience during the course of the PhD. At later project stages and in collaboration with postdocs, the student will also explore the in vivo role of the identified macrophage enhancers in atherogenic mouse models (ApoE ko, Ldlr ko, PCSK9).

What do we offer?
A creative and inspiring environment full of expertise and curiosity. Karolinska Institutet is one of the world’s leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. As a doctoral student you are offered an individual research project, a well-educated supervisor, a vast range of elective courses and the opportunity to work in a leading research group. Karolinska Institutet collaborates with prominent universities from all around the world, which ensures opportunities for international exchanges. You will be employed on a doctoral studentship which means that you receive a contractual salary. Employees also have access to our modern gym for free and receive reimbursements for medical care.

Eligibility requirements for doctoral education
In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline.

It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education.

A) General eligibility requirement
You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

  1. have been awarded a second-cycle/advanced/master qualification (i.e. master degree) or
  2. have satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the advanced/second-cycle/master level, or
  3. have acquired substantially equivalent knowledge in some other way in Sweden or abroad.*

Follow the instructions on the web page Entry requirements (eligibility) for doctoral education.

*If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education.

B) Specific eligibility requirement

You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:

- Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

Follow the instructions on the web page English language requirements for doctoral education.

Verification of your documents
Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action.

Skills and personal qualities
We are seeking a highly motivated and talented individual with a degree in molecular biology, biomedicine, medicine, biochemistry, genetics or related fields. Wet lab experience in state-of-the art molecular biology techniques applied to genomics, epigenomics and transcriptional regulation is required for this position. Desired is further someone who already is, or keen to become, familiar with the bioinformatics analysis of genome-wide sequencing data, in addition to above wet lab skills. Previous experience in studying metabolic-inflammatory disease pathways and/or macrophages/immune cells is a merit. The successful candidate is driven by a great curiosity for science, has excellent communication and organizational skills, and can work both independently and as a team player.

Terms and conditions
The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.
This is a KID faculty grant-supported full time position with salary and social benefits.

Application process
Submit your application and supporting documents through the Varbi recruitment system. Use the button in the top right corner and follow the instructions.

Your application should contain the following documents:

- A personal letter and a curriculum vitae (Swedish or English)
- Degree projects and previous publications, if any (Swedish or English)
- Any other documentation showing the desirable skills and personal qualities described above (Swedish or English)
- Documents certifying your general eligibility (see A above)
- Documents certifying your specific eligibility (see B above)

Selection
A selection will be made among eligible applicants on the basis of the ability to benefit from doctoral education. The qualifications of the applicants will be evaluated on an overall basis.

Karolinska Institutet uses the following bases of assessment:

- Documented subject knowledge of relevance to the area of research
- Analytical skill
- Other documented knowledge or experience that may be relevant to doctoral studies in the subject.

 All applicants will be informed when the recruitment is completed.

Want to make a difference? Join us and contribute to better health for all

Please apply via recruiter’s website.

Quote Reference: 340285