Understanding the genetics of blood cell formation
How do inborn genetic variation influences the blood and immune system in humans. What variations in our DNA sequence influence how our blood cells are formed and function? Which ones predispose for blood disorders (e.g., leukemia)?
This Ph.D. project aims to find regulators of blood cell formation using an innovative, population-genetic approach. Unlike traditional studies in vitro or in animal models, we exploit natural genetic variation between individuals to identify genes that regulate blood cell formation in vivo in humans. Instead of inserting artificial mutations in mice, we will read out ripples of the experiments nature has performed during evolution.
Building on unique sample streams, and the latest genomics and genome editing techniques, we will: (a) use large-scale, high-resolution flow cytometry data to find DNA sequence variants and genes that influence blood cell formation; and (b) investigate the functional role of these variants and genes. The project combines stem cell biology and human genomics. It differs from all previous population-genetic studies in the field in that the generated data will allow exploration of how genetic variation influences the formation not only of mature blood cells, but also at the stem- and progenitor cell stages.
The Ph.D. student will participate in a large-scale, collaborative effort (BloodVariome), involving researchers at Lund University and collaborating institutions, primarily deCODE Genetics (Reykjavik, Iceland). He/she will get an opportunity to work in strong research environments with a range of genomics techniques, including genome-wide association studies, next-generation sequencing, advanced flow cytometry, advanced bioinformatics, and CRISPR technology. The project will be supervised by senior researchers at Lund University and deCODE Genetics. The project will illuminate novel regulators of blood cell formation that are relevant in vivo in humans. Potentially, the results could be utilized in several areas in clinical hematology, including treatment of leukemias.
Lund University has one of Europe's strongest research environments for hematology. The environment involves about 250 researchers and students at the Biomedical Center (BMC). The research group is led by Professor Björn Nilsson, comprises about 15 individuals with complementary expertise (clinical, computational, experimental). The primary collaboration partner, deCODE Genetics, is a global leader in human genetics.
Special requirements: Must be interested in a Ph.D. in human genetics with a focus on blood cell formation, blood disorders, and cutting-edge genomics technologies. Must demonstrate solid training in human genetics, including a master degree in a relevant subject (e.g., genetics, molecular biology or similar). An understanding of bioinformatics and computing is preferred (but not a strict requirement). Must be highly motivated to work in a collaborative, international environment. Must have the ability and ambition to complete a Ph.D. that fulfils the requirements of the Medical Faculty at Lund University, and be willing to invest the effort needed
Understanding genetic predisposition for multiple myeloma
Multiple myeloma (MM) is the second most common blood cancer. While the causes are unknown, some cases are thought to have a heritable background. We recently identified DNA sequence variants that predispose for MM at 18 independent loci. However, it remains a mystery why these cause the disease.
In this project, we seek to understand the molecular effect DNA sequence variants that predispose for MM. For this, we will combine unique data sets from Sweden and Iceland with the latest genomics and genome editing techniques, including massively parallel sequencing, massively parallel reporter assays (MPRA), novel DNA binding assays and CRISPR-Cas9.
Specifically, the Ph.D. student will be enrolled in (a) extended genome-wide association studies to identify novel predisposition alleles; and (b) functional studies aimed at understanding the molecular mechanisms. Methodologically, the project will be based on advanced genotyping techniques (microarrays, sequencing and imputation) as well as advanced functional genomics and genome-editing techniques (e.g., MPRA and CRISPR-Cas9). The project will be directed by outstanding researchers at Lund University and deCODE Genetics in Reykjavik. The project will illuminate mechanisms that influence the risk of MM, increasing our understanding and abilities to control the disease.
The research group at Lund University, combines advanced mathematics and genomics to study malignant blood disorders and blood cell formation. The team is markedly multi-disciplinary and comprises 15 individuals with complementary skills, including clinical, computational, and experimental expertise. The scientific output includes publications in top-tier journals, as well as clinically implemented discoveries.