Seven researchers at KI appointed Wallenberg Academy Fellows
Seven young researchers connected to Karolinska Institutet have been appointed Wallenberg Academy Fellows 2016. The purpose of this program, funded by the Knut and Alice Wallenberg Foundation, is to boost Sweden as a research nation by retaining the greatest research talents in the country and by recruiting young international researchers to Swedish universities.
In all, 29 new Wallenberg Academy Fellows have been appointed this year, of which more than half have a foreign doctorate degree. The appointment process is conducted in collaboration with the Swedish universities and science academies, the Royal Swedish Academy of Sciences in particular, in the areas of natural sciences; social sciences, engineering and technology; humanities; and medicine. Funding is SEK 5 – 9 million per researcher for five years depending on the subject area.
These are the seven Wallenberg Academy Fellows at KI:
Topoisomerases are important cellular enzymes; they are involved in processes in which genes are copied, or when DNA is replicated prior to cell division. They unwind the DNA double helix, so that the enzymes that are going to transcribe genes or replicate DNA strands are able to do so. To stop the uncontrolled growth of cancer cells, it is now common to use pharmaceuticals that inhibit the topoisomerases’ activity. Cells are unable to divide if the DNA cannot be copied, which kills cancer cells. Unfortunately, these powerful drugs also affect other cells in the body that divide frequently, such as red and white blood cells.
Dr. Laura Baranello at the National Institutes of Health, Bethesda, USA, has studied topoisomerases in detail and made the ground-breaking discovery that their activity is stimulated by other enzymes in the cell. She will now continue to study the mechanism of regulation of topoisomerases, with the aim of developing topoisomerase inhibitors that selectively affect cancer cells. As a Wallenberg Academy Fellow, Laura Baranello will work at Karolinska Institutet’s Department of Cell and Molecular Biology.
Around 250,000 people in Sweden suffer from heart failure. This means that the heart has become so damaged that it no longer has the strength to pump enough blood around the body. It is possible to perform a heart transplant if the person is otherwise healthy, but many people who have heart failure die in a few years.
Dr. Olaf Bergmann at Karolinska Institutet’s Department of Cell and Molecular Biology aims to get damaged hearts to heal themselves. Previously, researchers thought that the heart only forms new cells during the fetal stage and childhood but, in 2009, Olaf Bergmann demonstrated, to many people’s surprise, that heart muscle cells are renewed throughout life.
He used a unique method for determining the age of the cells in an adult heart, utilizing the fact that nuclear weapons’ tests have changed the levels of carbon-14 in the atmosphere. As a Wallenberg Academy Fellow, Olaf Bergmann will continue to employ the latest technology in investigating the molecular mechanisms that stimulate cell growth in our hearts. The aim is to be able to control the process and encourage failing hearts to form healthy new cells.
Researchers had long thought that the natural killer cells, NK cells, found in the body’s various organs all had the same properties, but it has recently become clear that they are a mixed bag of cells that may even have different origins. As a doctoral student, Dr. Niklas Björkström studied the blood’s NK cells. In the project he is currently running at Karolinska Institutet’s Center for Infectious Medicine, he is investigating the NK cells found in the liver. As a Wallenberg Academy Fellow he will find out how they develop, how their activity is regulated and the role they play in steatohepatitis, a chronic liver disease in which the liver is fatty and inflamed, and during the development of tumors.
Niklas Björkström will also map the development of inflammation and cancer in the bile ducts. In order to study the immune cells of the bile ducts, which are deep in the body, he has developed a sensitive analysis technique that only requires a few thousand cells from his patients. More detailed knowledge of what governs inflammation in the liver and the bile ducts is necessary to be able to develop treatments for a number of fatal diseases.
There are many known risk factors for liver cancer, particularly chronic virus infections (hepatitis B and C), alcoholism and obesity. It is now the sixth most common form of cancer worldwide and the number of cases is increasing rapidly as a consequence of harmful lifestyle and environmental factors, among other things.
To better understand how liver cancer develops, Dr. Claudia Kutter, University of Cambridge, UK, will make detailed studies of the intricate mechanisms governing which genes in a cell are activated. People carry around 1500 proteins that form complexes with RNA molecules and regulate gene activity. Claudia Kutter will use the latest technology to map the interaction between RNA-binding proteins and RNA molecules, and how this affects gene expression in healthy and diseased cells.
Given that this disease is one of the deadliest forms of cancer, the project’s long-term aim is to find new pharmaceutical targets. As a Wallenberg Academy Fellow, Claudia Kutter will work at Karolinska Institutet’s Department of Microbiology, Tumor and Cell Biology. She is also a faculty member of SciLifeLab.
Embryonic stem cells are unique because they can form all the different cells in the human body. Dr. Fredrik Lanner at Karolinska Institutet’s Department of Clinical Science, Intervention and Technology is making basic studies of how the development of embryonic stem cells is governed in the early stages of the embryo. As a Wallenberg Academy Fellow, he will also investigate whether retinal cells produced from embryonic stem cells can be used to treat macular degeneration, an eye disease that affects nearly one in five people over the age of 65.
In his previous research, Fredrik Lanner developed well-functioning retinal cells, but to be able to use them in studies involving people, the stem cell lines must be produced in ultra-clean cell culture rooms in accordance with standards for pharmaceutical production. Fredrik Lanner has initiated the KI Stem Cell Bank in order to produce clean stem cells. The aim is to collect at least 150 different cell lines that match patients with differing HLA. If the HLA type in the transplanted cells matches the patient’s own, it reduces the risk of the immune system rejecting the transplanted cells. In the future, the stem cells in the KI Stem Cell Bank may be used to develop all the types of cells in the body.
Our red and white blood cells are continually renewed. Stem cells in the bone marrow divide and, based on these, all the specialized cells found in our blood are formed: monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, T cells, B cells and NK cells.
To better understand this basic process in our bodies, Dr. Sidinh Luc from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, USA, will, among other things, isolate different types of blood stem cells and mark them using gene-technology tools. This mark will then reveal which specialized blood cells originate from which stem cell.
Sidinh Luc will also investigate how epigenetic differences govern the development of different blood stem cells and how levels of various stem cells in the bone marrow change throughout life. The hope is that more detailed knowledge of blood formation will increase understanding of how different forms of blood cancer develop and how they can be treated. As a Wallenberg Academy Fellow, Sidinh Luc will move her work to Center for Hematology and Regenerative Medicine at Karolinska Institutet.
Vicente Pelechano García
Bet-hedging is a term used by evolutionary biologists to describe the ability of microorganisms to adapt to unpredictable surroundings, where genetically equivalent organisms can develop different characteristics. For example, in a bacterial infection, some of the bacteria may develop resistance to a particular antibiotic, despite genetic analysis showing that they should be responsive to it. Researchers have also recently shown that similar processes can explain some cancer cells’ resistance to chemotherapy.
Dr. Vicente Pelechano García, Karolinska Institutet, will study what allows cells to react differently to a particular pharmaceutical. As a Wallenberg Academy Fellow, he will investigate subtle differences in the packaging of the long strands of DNA and how this affects the expression of various genes. Differences in gene expression may also occur when a gene is copied to messenger RNA, which in turn affects the shape of the protein that is formed from the gene. A better understanding of these fundamental processes in the cell is necessary for researchers to be able to develop treatments that are effective against all cancer cells and microorganisms – even those that are most resilient.
Research presentations: The Royal Swedish Academy of Sciences
Photo credit: Markus Marcetic