PhD position in immunology, using single-cell genomics, in the Reinius lab at Karolinska Institutet.

Do you want to contribute to improving human health?

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 research group of Björn Reinius is part of the Division of Biomaterials at the Department for Medical Biochemistry and Biophysics , located at the newly built Biomedicum research laboratory at the Solna campus of Karolinska Institutet (KI), Stockholm, Sweden.

The group uses a multi-disciplinary approach integrating methods development for RNA/DNA sequencing (particularly aimed at the single-cell resolution), bioinformatics, molecular biology, cell-culture and animal models, to characterize and understand the mechanisms of gene regulation in mammals. A special focus of the lab is dosage compensation of sex chromosomes. During the past years, Reinius and colleagues pioneered the use of single-cell RNA-seq in the context of X-chromosome regulation (Science 2014, Nature Genetics 2016, Cell 2016, Nature Structural and Molecular Biology 2019, Nature Communications 2020 etc., see lab homepage). The Reinius lab is equipped with all components needed for executing state-of-the-art research in the topic, including cell and animal systems, molecular biology resources and equipment, access to high-throughput sequencing machines, and capacity for computation-intense analyses (a dedicated computational server is available within the lab).

The Reinius lab furthermore develops technological solutions with real-world impact on clinical diagnostics and laboratory procedures applications. Examples of this is the development of an RNA-extraction-free Covid-19 diagnostic method used in >3.5 million clinical tests in Sweden and the creation of the KI-spin-off company SEQURNA AB which supplies research reagent globally. The facility wherein the lab is located, Biomedicum, provides a vibrant international research environment and in-house access to core facilities, lectures by world-leading scientist, and excellent seminar series. Reinius is the Head of the Division of Medical Systems Bioengineering.

Applications are invited for a position in the Björn Reinius group, funded by the Karolinska Institute and Knut & Alice Wallenberg Foundation. The appointment will be on a temporary basis for a period of 4 years (PhD student), starting late 2025 or early 2026. If you have any questions, do not hesitate to write to: bjorn.reinius@ki.se

The PhD student will be Co-supervised by Christoph Ziegenhain (KI), Nils Landegren (Uppsala University), and Marie Wahren-Herlenius (KI).

The doctoral student project and the duties of the doctoral student

Functional analysis of fundamental drivers of immunological sex differences

Background and overarching goals: Autoimmune diseases affect ~5% of the population, entailing high morbidity and increased mortality rates. Women are at much higher risk of developing autoimmune disease, with the most extreme numbers in systemic disorders such as SLE and Sjögren’s syndrome for which >90% of patients are women. Effects of sex hormones, X-chromosome dosage, and sexually dimorphic autosomal gene regulation underlie the sex bias, but the molecular basis for sex differences in immune regulation is far from understood.

A deeper understanding of the factors controlling immunological sex differences is warranted, and how these factors lead to autoimmune disease. Fundamentally, biological sex differences ultimately stem from the sex chromosome complement (XX/XY). However, most dimorphisms are not direct effects of X/Y genes, but from activational effects of gonadal steroid hormones occurring during adolescence and adulthood, mainly excreted from reproductive tissues.

To dissect genetic and hormonal contributions to sex-dependent immune regulation, the PhD student will utilize unique human cohorts of women and men undergoing gender reassignment by sex hormone treatment, and samples from individuals who are cellular mosaic for sex chromosome karyotypes. These unique human studies are directly useful for understanding medically relevant sexual dimorphisms, however, inherently limited in that only peripheral parts of the immune system can be analyzed without invasive procedures on the subjects.

Fortunately, in this context, the main drivers of sexual determination and differentiation are evolutionarily conserved among therian mammals, i.e. sex chromosome structure (XX/XY), the sex determination factor (the Sry gene located on chrY, initiating testes formation), and the main hormonal cascades following gonadal formation (Capel Nat Rev Genet 2017). To uncover fundamental sex differences in the immune system and to identify the molecular drivers underlying them, the student will employ a remarkably useful mouse model system, the “Four Core Genotype” (FCG) (De Vries J Neurosci 2002), in which the effects of gonadal sex and secreted hormones are disconnected from the sex chromosomes of the individual. 

Strategic considerations of the doctoral research project: The research plan is composed to provide a multifaceted research experience for the PhD student in fields of biomedicine, including work on animal and human systems, exposure to various state-of-the-arts techniques, and provides a balanced risk level considering the different objectives. The proposed plan constitutes a part of a large research project that was recently granted financial support from the Knut and Allice Wallenberg Foundation (Wahren-Hernelius, Kämpe, Reinius, Landegren), placing the student in solid and collaborative research context. Objective 1 will be performed in the Reinius lab (MBB, KI – the PhD student’s home department) in collaboration with Christoph Ziegenhain (MBB, KI), and Objective 2 will be performed in collaboration with Landegren (Dept. Medical Biochemistry and Microbiology, Uppsala University) and Wahren-Herlenius (Dept. Medicine, KI).

Educational outcome and responsibilities
The successful applicant will gain both foundational and specialized knowledge in gene regulation, chromatin biology, RNA biology, embryonic development, and stem cell biology. The project involves applying, mastering, and further developing in silico and/or wet-lab research methodologies within the fields of transcriptomics, next-generation sequencing, and bioinformatics, which are core areas of expertise in the group.

Skills to be acquired include state-of-the-art molecular biology techniques (with emphasis on high-throughput sequencing and single-cell omics), cell culture (particularly stem cells), animal science research, and bioinformatics (focusing on RNA/DNA sequencing data analysis).

The PhD student is expected to take an active and independent role in project design, management, data generation, analysis, and interpretation. Additional responsibilities include collaborative teamwork, maintaining high scientific and ethical standards, and contributing to a dynamic, interdisciplinary and international research environment. A strong commitment to continuous professional development is essential.

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.

(A) and (B) can only be certified by the documentation requirement for doctoral education.

Skills and personal qualities

We are looking for an enthusiastic and highly motivated candidate who has a degree in Genomics, Bioinformatics, Molecular Biology, Biomedicine, or Biochemistry. Proven experiences in RNA biology, gene regulation, transcriptome-wide studies, mammalian cell or tissue culture techniques, animal science, bioinformatics and programming for statistical computing are particularly advantageous. A strong interest in interdisciplinary experimental method development and creative thinking abilities are essential. Applicants wishing to integrate computational and experimental biology approaches are especially encouraged to apply.

The ideal candidate should be collaborative, scientifically adventurous, curiosity-driven, and should bring independent and original ideas into the project. Any previous records of independent research as well as productive interactions within a multi-disciplinary team environment (e.g. first- or co-author publications) are advantageous. Since the applicant will work in a multidisciplinary environment the ability to work with other scientist and good communication skills (proficiency in spoken and written English) are necessary. Since some of our experiments are performed on cells and tissues derived from mouse, the applicant must be willing to perform animal research.

Terms and conditions

The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.

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. We prefer that your application is written in English, but you can also apply in Swedish.

Your application must contain the following documents:

- A personal letter and a curriculum vitae
- Degree projects and previous publications, if any
- Any other documentation showing the desirable skills and personal qualities described above
- 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.

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