Project 1
Improving heart regeneration in zebrafish using virus mediated gene regulation.
The Andersen group (https://www.sdu.dk/dca) branches out from the department of Clinical Biochemistry at Odense University Hospital (OUH) and is part of Clinical Institute, University of Southern Denmark. Overall, our lab utilizes regenerative medicine to improve heart regeneration and executes both basic and clinical research from zebrafish and mice to man.
It is generally accepted that the mammalian heart is non-regenerative after myocardial infarction (MI) explaining why MI is one of the largest causes of death globally. By contrast, zebrafish have an amazing capacity to regenerate the heart following damage through cardiomyocyte (CM) renewal. Zebrafish thus represent excellent models to study heart regeneration after injury. We have by single cell RNA sequencing identified candidate master gene regulators of CM proliferation, and would now like to confirm this. In this project, the student will therefore determine the effect of certain master transcription factors on regenerative mechanisms of zebrafish CMs, and hereby contribute new knowledge that may be translated into adult mammalian CMs with the aim of inducing CM renewal and heart regeneration after myocardial infarction (MI) in man. A long-term perspective of this would be that the CM loss after MI can be compensated thereby rescuing the heart pump function improving patient life quality and reducing mortality.
The student will accomplish the aim by viral mediated gene regulation in vivo using adeno associated virus (AAV) injections in zebrafish with and without heart apex resection injury. EdU will be injected in parallel to enable quantification of in vivo CM proliferation. As such the student will handle zebrafish including household, perform AAV and EdU injections as well as surgery in zebrafish using microscopy. He/she will produce AAV virus encoding transcription factors, and perform qRT-PCR and immunohistochemistry to visualize the effect after heart and organ removals. The student will also acquire skills in writing and be part of DCA group, where we all strive to reach the same goal working as a solid team and making all projects synergetic.
The lab is physically located in Winsløwparken 25. Check out our website (https://www.sdu.dk/dca), send an email (dandersen@health.sdu.dk) or pass by for an unformal discussion on science and project opportunities.
Main supervisor and co-supervisor: Professor Ditte C. Andersen and postdoc Ditte Gry Ellman.
Project 2
Investigating heart regeneration in zebrafish using cryoinjury.
The Andersen group (https://www.sdu.dk/dca) branches out from the department of Clinical Biochemistry at Odense University Hospital (OUH) and is part of Clinical Institute, University of Southern Denmark. Overall, our lab utilizes regenerative medicine to improve heart regeneration and executes both basic and clinical research from zebrafish and mice to man.
It is generally accepted that the mammalian heart is non-regenerative after myocardial infarction (MI) explaining why MI is one of the largest causes of death globally. By contrast, zebrafish have an amazing capacity to regenerate the heart following damage through cardiomyocyte (CM) renewal. Zebrafish thus represent excellent models to study heart regeneration after injury. Hereto, we have used apex resection (AR) in the zebrafish heart to study heart regeneration. Yet, cryoinjury and the processes of heart remodeling is more similar to what occurs in humans after MI. The student will therefore setup the cryoinjury model in zebrafish, and determine the rate of CM proliferation in 3D heart views. This will be an important new method for the research field to be exploited for identifying mechanisms that may improve heart regeneration.
The student will handle zebrafish including household, perform substantial heart surgery in zebrafish using microscopy. He/she will use qRT-PCR, immunohistochemistry, tissue clearing and particular confocal imaging to create 3D views of the regenerating heart at different timepoints after surgery. The student will also acquire skills in writing and be part of DCA group, where we all strive to reach the same goal working as a solid team and making all projects synergetic.
The lab is physically located in Winsløwparken 25. Check out our website (https://www.sdu.dk/dca), send an email (dandersen@health.sdu.dk) or pass by for an unformal discussion on science and project opportunities.
Main supervisor and co-supervisor: Professor Ditte C. Andersen and postdoc Ditte Gry Ellman.
Project 3
How does imprinting affect cardiomyocyte differentiation of induced pluripotent stem cells?
The Andersen group (https://www.sdu.dk/dca) branches out from the department of Clinical Biochemistry at Odense University Hospital (OUH) and is part of Clinical Institute, University of Southern Denmark. Overall, our lab utilizes regenerative medicine to improve heart regeneration and executes both basic and clinical research from zebrafish and mice to man.
The human heart is unable to regenerate lost cardiomyocytes after damage such as myocardial infarction, leading to reduced pump function and ultimately heart failure. Stem cells have the ability to differentiate into all other cell types in the body, and may aid in forming new cardiomyocytes, however our recent understanding is that the heart lacks stem cells. Yet, most recent advances in induced pluripotent stem cell (iPSC) technology have given new hope for a feasible near-future therapy. iPSC can be derived from a somatic cell from a donor, e.g. skin or blood, and be reprogrammed back into an embryonic pluripotent state that enables derivation of an unlimited source of any sought after cell type for therapeutic purposes, in this case cardiomyocytes. Despite the huge potential of iPSC derived CMs, there is still a lot we don’t know and more knowledge on the underlying mechanisms may help improve iPSC-CM translations into the clinic. Imprinting is a well-known key player in tissue and organ development, and we have identified an imprinted gene that may affect the cardiomyocyte derivation process. The student will therefore investigate the role of this imprinted gene during cardiomyocyte differentiation from iPSC.
The student will investigate this by studying iPSCs with a CRISPR mediated knock-out of the gene of interest. This entails learning how to culture iPSC and derive these into cardiomyocytes. Furthermore, multiple techniques will be used to characterize the effect of the imprinted gene on the iPSC-cardiomyocytes, including immunohistochemistry, qRT-PCR and flow cytometry. The student will also acquire skills in writing and be part of the DCA group, where we all strive to reach the same goal working as a solid team and making all projects synergetic.
The lab is physically located in Winsløwparken 25. Check out our website (https://www.sdu.dk/dca), send an email (dandersen@health.sdu.dk) or pass by for an unformal discussion on science and project opportunities.
Main supervisor and co-supervisor: Professor Ditte C. Andersen and postdoc Sabrina Bech Mathiesen.
Project 4
Endoreplication as a way to adjust mouse development
The Andersen group (https://www.sdu.dk/dca) branches out from the department of Clinical Biochemistry at Odense University Hospital (OUH) and is part of Clinical Institute, University of Southern Denmark. Overall, our lab utilizes regenerative medicine to improve heart regeneration and executes both basic and clinical research from zebrafish and mice to man.
It is well known that the mammalian organism grows by cell proliferation and then at some point after birth starts switching to undergo hypertrophy or cell enlarging instead until the body is fully grown. A recent theory has emerged suggesting that endoreplication (DNA doubling without cell division) is a way for some tissues like skeletal muscle and the heart to self-limit proliferation while forcing terminal differentiation. We have recently in the heart identified a transcription factor (TF) which induces polyploidy through endoreplication. We would now like to investigate whether this factor ensures polyploidy to sustain high production of RNA and proteins required for the high muscle work of fully differentiated heart- and skeletal muscles. This may provide new knowledge to be used both for developing therapies for both heart and skeletal muscle disease.
The student will examine different organs from neonatal mice which have been manipulated for the candidate TF using adenovirus injection immediately after birth. Moreover, the candidate TF will be used in vitro to assess the effect on skeletal and heart muscle cells to evaluate the effect on proliferation and hypertrophy.
The student will perform sectioning of tissue, immunohistochemical staining and associated microscopy. Moreover, the student will culture cells, produce viruses, and perform immunocytochemistry, qRT-PCR and flow cytometry. The student will also acquire skills in writing and be part of DCA group, where we all strive to reach the same goal working as a solid team and making all projects synergetic.
The lab is physically located in Winsløwparken 25. Check out our website, send an email (dandersen@health.sdu.dk) or pass by for an unformal discussion on science and project opportunities.
Main supervisor and co-supervisor: Professor Ditte C. Andersen and postdoc Ditte Gry Ellman
Project 5
The role of a candidate transcription factor in cardiomyocyte derivation from induced pluripotent stem cells
The Andersen group (https://www.sdu.dk/dca) branches out from the department of Clinical Biochemistry at Odense University Hospital (OUH) and is part of Clinical Institute, University of Southern Denmark. Overall, our lab utilizes regenerative medicine to improve heart regeneration and executes both basic and clinical research from zebrafish and mice to man.
It is generally accepted that the mammalian heart is non-regenerative after myocardial infarction (MI) explaining why MI is one of the largest causes of death globally. One of the reasons is likely the hearts inability to replenish dead cardiomyocytes lost to injury. Induced pluripotent stem cell (iPSC) technology is thus a viable option to obtain cardiomyocytes in the lab for treatment of cardiac patients. iPSC can be derived from a somatic cell from a donor, e.g. skin or blood, and be reprogrammed back into an embryonic pluripotent state that enables derivation of an unlimited source of any sought after cell type for therapeutic purposes. Despite the huge potential of cardiomyocytes differentiated from iPSC (iPSC-CMs), the current iPSC-CMs we are able to make in the lab are immature and resemble fetal more than adult cardiomyocytes. Injection of too immature iPSC-CMs can lead to suboptimal integration into the patient’s heart and cause complications like arrythmias. Thus, substantial effort is put into maturing the iPSC-CMs to obtain better cells for the patients. In the DCA-lab we have previously identified a candidate transcription factor (TF) as an important player during cardiomyocyte development, especially in the regulation of cardiomyocyte cell cycling.
In this project the student will explore the role of the candidate TF during the cardiomyocyte differentiation of iPSCs. Especially whether the candidate TF can affect maturation of these cells. This entails learning how to culture iPSC and differentiate these into cardiomyocytes. Expression of the candidate TF will be manipulated via adeno-associated viral (AAV) vectors. Furthermore, multiple techniques will be used to characterize the effect of the candidate TF on iPSC-CMs, including qRT-PCR and immunohistochemistry. The student will also acquire skills in writing and be part of the DCA group, where we all strive to reach the same goal working as a solid team and making all projects synergetic.
The lab is physically located in Winsløwparken 25. Check out our website, send an email (dandersen@health.sdu.dk) or pass by for an unformal discussion on science and project opportunities.
Main supervisor and co-supervisor: Professor Ditte C. Andersen and postdoc Sabrina Bech Mathiesen
Project 6
In vivo transplantation of induced pluripotent stem cells
The Andersen group (https://www.sdu.dk/dca) branches out from the department of Clinical Biochemistry at Odense University Hospital (OUH) and is part of Clinical Institute, University of Southern Denmark. Overall, our lab utilizes regenerative medicine to improve heart regeneration and executes both basic and clinical research from zebrafish and mice to man.
It is generally accepted that the mammalian heart is non-regenerative after myocardial infarction (MI) explaining why MI is one of the largest causes of death globally. Different types of stem cells have been investigated for their ability to contribute to regeneration of the lost myocardium, however none of these have truly regenerated the myocardium. Therefore, the recent advances in induced pluripotent stem cells (iPSCs) technology have given a promising candidate for heart regeneration, however there are still many challenges that must be solved. One obstacle is the survival of iPSCs after transplantation. In this study, the student will therefore investigate the presence of iPSCs in mouse tissue following transplantation. iPSCs will first be transplanted to an easily accessible tissue and, then depending on the results into the heart.
For this project the student will take part in growing the iPSCs, assist in transplantation of iPSCs to mice and collection of the tissue following, hence a course in handling of laboratory animals will be an advantage, the surgeries themselves will be performed by persons with extensive experience within this field. In addition, the student will perform sectioning of tissue, immunohistochemistry, imaging, and in the end analyze results. The student will also acquire skills in writing and be part of DCA group, where we all strive to reach the same goal working as a solid team and making all projects synergetic.
The lab is physically located in Winsløwparken 25. Check out our website, send an email (dandersen@health.sdu.dk) or pass by for an unformal discussion on science and project opportunities.
Main supervisor and co-supervisors: Professor Ditte C. Andersen and postdoc Sabrina Bech Mathiesen and postdoc Ditte Gry Ellman