ISCOMS Research Fellowships

Supervisor: Lydia Visser MD PhD working with three PhD-students with an MSc

Field of research: Pathology and Medical biology

Description: We will look at different aspects of lymphoma research by looking at the expression of proteins, drug sensitivity, combination therapy, or effect on the microenvironment. We can use techniques such as immunohistochemistry, cell culture, flowcytometry, western blot, elisa and metabolic assays. There will be different projects.

Experience from student: Looking for a student with interest in labwork

Supervisor: Jaap van den Born MD PhD, prof. Stefan P. Berger MD PhD

Field of research: Nephrology 

Description: In Nephrology Dept. various projects are running using diverse methodologies (see 1-6). You are invited to express your interests in one of these fields (being either clinical, epidemiological, human- or animal in vivo- or in vitro experimental) to indicate what sub-project interests you most. Please motivate your interest in the specific topic.

1. Patients with renal disease and progressive renal function loss, are being studied with respect to the mechanisms via which the urinary protein leakage results in renal function loss. We aim to modulate proteinuria-driven complement activation on endothelial and tubular cells.
2. Our center also has a large population of renal transplant recipients. These patients are monitored very closely, and regimens aimed at increasing the duration of graft function as well as patient survival are being studied currently. A large database including biobanked urine and plasma is available in TransplantLines. Within this cohort we try to entangle which factors associate/contribute to transplant loss and mortality.
3. General population cohorts are studied to detect which parameters lead to initiation of progressive renal function loss and its complications. The cohorts PREVEND and Lifelines from the general population are good examples. The natural course is followed to study possible causes of morbidity and mortality in relation to renal parameters.
4. Lifestyle and the kidney. Many lifestyle factors are involved in the risk of long term renal function loss. These include smoking as well as nutritional habits, such as excess caloric intake leading to obesity and diabetes, excess sodium intake and sedentary lifestyle. The mechanisms of renal damage induced by these lifestyle factors are being studied in patients as well as experimental animals, and the effect of lifestyle intervention measures on the course of renal disease is being studied. Nutritional monitoring is part of this project.
5. Endothelial dysfunction highly contributes to progression of renal and cardiovascular diseases. We are interested in the effects of uremic and/or transplantation conditions on the endothelial glycocalyx, and functional consequences of endothelial injury. This work is performed on human (renal) endothelial cells in culture and tissues from renal patients.
6. Immunity and the kidney. Within this research line we try to unravel the role of the immune system (complement system, leukocytes, endothelial cells) in chronic renal damage in proteinuric and transplanted kidneys. B-cell, endothelial and complement profiling will be associated with clinical outcome parameters.

Experience from student: Interest in nephrology 

Supervisor: Prof. Ton Lisman PhD, Silke Bodewes MD PhD-student

Field of research: Surgery

Description: At the UMCG, we employ normothermic machine perfusion (NMP) for the evaluation of initially declined donor livers. NMP allows us to assess the viability of the liver and bile ducts, while the liver is fully metabolically active. To gain insights into these processes, we collect liver parenchyma biopsies before and after NMP. We aim to visualize multiple protein markers simultaneously using immunofluorescent staining and microscopy. During this project, students will learn the techniques of slicing liver biopsies, performing immunofluorescent staining, and evaluating the stained biopsies. If a liver perfusion is ongoing during the Research Fellowship, students may have the opportunity to observe the process.

 Experience from student: Looking for a student with laboratory experience.

Supervisor: Prof. Adriaan Voors MD PhD, Erik Lipsic, MD PhD, Chris Lenselink BSc

Field of research: Cardiology 

Description: The employment of percutaneous coronary intervention (PCI) as first-line treatment for ST-elevation myocardial infarction (STEMI) has resulted in a preserved systolic function, as reflected by left ventricular ejection fraction, in the majority of patients. However, adverse diastolic remodeling is emerging as a predictor of clinical outcome as well. In spite of this, little is known about the pathophysiology of diastolic dysfunction after STEMI. In a prominent hypothesis, dysfunction of the coronary microcirculation, the tiniest vessels in the heart, is a pathophysiological hallmark of diastolic dysfunction. There is an unmet need to easily, objectively, and quickly assess the status of the coronary microcirculation during the PCI procedure of STEMI patients. The myocardial blush grade (MBG) is a potential marker for coronary microvascular dysfunction (CMD), yet it is not objective with high intra- and interobserver variability.

Objective: To investigate the association of automated MBG scores and diastolic function in STEMI patients.

Methods: Non-diabetic STEMI patients from the GIPS-III trial will be analyzed. Automated MBG scores will be calculated using the QuBE software which semi-automatically determines MBG values using coronary angiograms as recorded during the PCI procedure. Diastolic function will be determined by abnormal results on echocardiography performed shortly after STEMI as well as after 4 months follow-up. Diastolic dysfunction will be defined as abnormal E/e’ ratio and left atrial reservoir strain values, using 40 patients with diastolic dysfunction and 40 without. Using linear regression modeling, we will investigate whether automated MBG values are associated with abnormal diastolic function at baseline as well as change in diastolic function over the follow-up period.

Experience from student: Basic knowledge about statistics and coronary anatomic knowledge.

Supervisor: Alexandra Androni PhD-student

Field of research: Medical education 

Description: This project aims to validate a student engagement observation instrument by assessing its validity and inter-rater reliability. The student will work with previously collected data, whereby researchers used an observation instrument to score student engagement behaviour. Since this is a non-clinical project, emphasis is focused on educational theories, literature in educational models and instruments used to measure student engagement in higher education. We will begin by examining medical education literature and we will then discuss the current observation instrument that was used during data collection. The student will afterwards study the data and propose a method to validate sub-categories of the instrument. Validation strategies that we could work on might be content-related, construct-related or criterion-related.The research question that the student will try to answer will be adapted according to the student’s interests and competences, but will be related to the validation of the student engagement observation instrument. It is preferable that you are familiar with basic statistics (SPSS, STATA, etc.), and that you have some experience with quantitative research.

Finally, you will gain experience working in an inter-disciplinary team of medical education researchers, you will learn about the process of applying and attending medical school at the University of Groningen and you will work on your skills combining qualitative and quantitative research methods!

Experience from student: basic statistical knowledge and quantitative research.

Supervisor: Sebo Withoff PhD

Field of research: Genetics ERIBA 

Description: The Immunogenetics group of the Department of Genetics within the UMCG investigates the role of genetic variation in health and the aetiology of autoimmune diseases (e.g. coeliac disease), the role of the gut microbiome therein, and is generating iPSC-based organ-on-chip models to investigate and validate ‘omics’ findings. 

The data for these studies are mostly generated by next generation sequencing such as single-cell RNA-seq and ATAC-seq. The generation and analyses of the data requires a broad range of scientific expertise. In our group, a dynamic and highly interactive environment is created in which bioinformaticians, geneticists, statisticians, molecular biologists, stem cell biologists and immunologists work together closely. 

 Important findings published by the group are (a) the shared genetics of autoimmune diseases, (b) 95% of the autoimmune disease-associated single nucleotide polymorphisms (SNPs) affect gene expression rather than gene function, (c) eQTL effects of GWAS SNPs on long non-coding RNAs (lncRNAs), and (d) a range of environmental factors affecting the human microbiome. 

 The current ongoing research is for a large part focused on the prioritisation of SNPs, genes, pathways and cell types affected in autoimmune diseases, on in vitro experiments to validate the function of the prioritised candidates and on determining how host genetics affects microbiome composition. 

 Depending on the background and interests of the student, we will design a working plan for the two-week internship. 

Supervisor: Christian Hulzebos MD PhD

Field of research: Neonatology 

Description: Neonatal jaundice is a condition of elevated bilirubin level, also known as hyperbilirubinemia. Severe hyperbilirubinemia is potentially dangerous, and – when left untreated – may cause permanent brain damage. To prevent the harmless condition of neonatal jaundice from developing into kernicterus, it is highly important to identify the children at risk at an early stage. Jaundice can be identified by visual examination due to its ability to give yellowish colour to the skin and sclerae of the eye. However, visual judgement of jaundice severity has proven to be unreliable, even though performed by experienced health personnel. The measurement of bilirubin is traditionally done by blood samples. To reduce the need of drawing blood from the newborn, transcutaneous bilirubinometers have been developed to measure the bilirubin  in the newborn skin. Both laboratory equipment and transcutaneous bilirubinometers are rather expensive, with a price of 6-10.000 US dollars, thus making them practically unavailable in low-income countries. Since most deaths due to jaundice occur in low-income countries, there is a large unmet need of simple, reliable and affordable technologies to identify at-risk newborns.  There is a novel instrument that may fulfil these requirements: a smartphone-based application that estimates bilirubin levels based on the colour analysis of a digital image.

We hypothesise that the smartphone app in estimating bilirubin levels is highly correlated to transcutaneous or serum bilirubin levels, and that this new method is better than the visual estimation of neonatal jaundice. Following our hypothesis, the short-term goal for this project is to assess the user friendliness and hopefully demonstrate the ability of this novel screening method to identify newborns with neonatal jaundice.

Supervisor: Prof. M.H. de Borst, MD, PhD, C.J. van Lieshout, MD PhD

Field of research: Nephrology 

Description: Chronic kidney disease (CKD) forms a major medical, social and economic burden with a high risk of morbidity and premature mortality, affecting approximately 10% of the global population. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are cornerstone therapy in patients with CKD. At the same time, <50% of patients with advanced CKD are on ACEi/ARB therapy. Several factors, including hyperkalaemia, can lead to discontinuation of ACEi/ARB in advanced CKD, and discontinuation of ACEi/ARB has been associated with an increased risk of cardiovascular disease, kidney failure or death. The main hypothesis of this trial is that the potassium binder patiromer enables up-titration of ACEi/ARB treatment in patients with CKD stage 3b/4 who are on suboptimal ACEi/ARB therapy and prone to hyperkalaemia, resulting in a reduction in albuminuria and blood pressure. We will investigate this hypothesis in a randomized, double-blind, placebo controlled cross-over trial. You will get familiar with all that it takes to perform a clinical trial.

Supervisor: Prof. Cor Calkhoven MD PhD, PhD-student Clément Karch 

Field of research: ERIBA, Ageing biology 

Description: Breast cancer is one of the most prevalent cancers worldwide. Breast cancer can be classified into different subtypes requiring different treatment, and despite the existence of treatments for most types of breast cancers, prognosis for metastatic breast cancer is still poor. To develop more specific and effective treatment it is crucial to understand the underlying cellular and molecular mechanisms that specify a certain breast cancer subtype.

The transcription factor C/EBPβ-LIP is specifically overexpressed in triple-negative breast cancer and was shown to be involved in cell migration, cancer metabolism and possibly immune evasion. The student will work on aspects of oncogenic functions of C/EBPβ-LIP. The project will likely involve cell culture, transfection, and immunoblotting techniques as well as assays for cancer cell proliferation and survival.

Experience from student: some laboratory experience in molecular biology

Supervisor: Sandra Hein MD

Field of research: Radiology

Description: Research has shown that in the Netherlands deaf people have less access to health care. This limited access to healthcare probably arises from communication barriers and a lack of cultural awareness among medical practitioners. This innovative project aims to explore and compare the knowledge of medical students and health professionals regarding the healthcare accessibility of deaf individuals. 

Project 

During the spring 2024, we will conduct a survey among medical students and professionals. This survey will gather information about their knowledge about deaf peopl, their culture, if they think it is necessary to learn more about this barrier between the hearing and deaf culture in the curriculum etc. 

In this research fellowship, you will conduct the same survey in your country with the same respondents. Also, you will do some literature research or local research on how the situation in your country is for deaf people. 

This project differs from the others, as you should spread the survey among medical students and/or professionals before ISCOMS starts! (This will give you more time during the IRF and give you more time to discover the lovely city of Groningen).

We are looking for several students from different countries who are interested in this subject, so we can compare all the outcomes of the different situations/countries. 

Practical 

We can go to our local sign language bar and order food in Dutch sign language. You are welcome to our radiology/nuclear medicine department and have a look at multiple modalities. There will be an ultrasound workshop (you can perform the ultrasound at each other, try to give instructions in signs, not words). You can meet the research staff if you have any questions and work closely together with the anatomy section. You can make it your own project with supervision from researchers of the UMCG. 

After this project, we hope that you can come up with suggestions about how we can improve the accessibility to medical care for deaf patients. How can we break the silence?!

Supervisor: dr. Nynke Smidt, Rosa Palazuelos Gonzalez PhD-student

Field of research: Epidemiology 

Description: Mental health is paramount for overall well-being, yet persistent conditions such as depression (affecting approximately 5% of adults) and anxiety disorders (impacting 4% of the total population) continue to challenge global preventive efforts. These conditions can significantly impact daily activities. While increasing physical activity is recognized as a beneficial strategy in preventing and treating depression and anxiety, current research often emphasizes in high-intensity exercises. Unfortunately, this focus often neglects the significance of other movement behaviors that might be performed in higher amounts of time throughout the day, such as sedentary activities and sleep.

This project aims to address this gap by examining the time allocated to various movement behaviors among adults in the Lifelines cohort. By exploring the prevalence of major depression and anxiety, the study seeks to identify specific activities associated with these mental health conditions. Recognizing the interrelation of daily activities, isotemporal substitution analysis will be employed to identify the impact of replacing time in one or other activity on mental health.

The research process involves a review of the latest literature, and regular meetings to discuss and interpret the results of the statistical analyses. The primary objective is to produce a draft manuscript. While prior experience in scientific writing is recommended (though not mandatory), this project provides a unique opportunity to contribute to the understanding of how daily movement behaviors impact mental health.

Experience from student: Basic statistical knowledge of logistic regression models is needed to interpret the obtained results from the performed analysis 

Supervisor: prof. dr. Inge S. Zuhorn, Ginevra Mariani PhD-student

Field of research: Biomedical Technology

Description: Glioblastoma is a highly aggressive type of brain cancer with a short survival period after treatment, which indicates a pressing need for better treatment options. 

Nanoparticles (NPs) can be loaded with therapeutic molecules which significantly enhances their pharmacokinetics, biocompatibility and biodistribution, making NPs good candidates for the treatment of disease. However, to effectively reach the target site in the brain, NPs have to overcome many obstacles, like clearance from blood circulation, crossing of the blood-brain barrier and entering target brain cells. 

This project focuses on the development and characterization of a library of nanogels with different sizes and stiffnesses for the identification of optimal properties to overcome the above-mentioned obstacles. Nanogels are soft colloidal particles consisting of a crosslinked polymer network with tuneable properties, high biocompatibility and high loading capacity for hydrophilic drugs, such as DNA, RNA, proteins and peptides. 

Poly(N-isopropylmethacrylamide) (p(NIPMAM)) nanogels are synthesized by precipitation polymerization. Nanogel properties such as size, charge and morphology will be investigated using different techniques, including dynamic light scattering, zeta potential measurement, atomic force microscopy and nanoparticle tracking analysis. Subsequently, the nanogels will be tested for increased blood circulation time, transport across the BBB and penetration into tumour spheroids.

Experience from student: Knowledge of nanotechnology or biology 

Supervisor: prof. Marco Demaria, dr. Boshi Wang

Field of research: Cellular senescence and age-related pathologies

Description: Sex is still often considered a confounding factor rather than biological variation in cancer and aging studies, limiting our understandings of basic biological processes and differential sex-dependent responses to drug treatment. Sex chromosome-linked genes and sex-specific hormones play crucial roles in cancer- and aging-related phenotypes, but numerous data suggest that additional sex-associated cellular and molecular mechanisms are implicated.

Senescent cells play crucial roles in cancer and aging, and they are generally characterized by the upregulation of Cyclin-Dependent Kinase (CDK) inhibitor p16. Using this feature, our lab has developed the p16-3MR mouse model to selectively isolate, visualize and kill senescent cells. Using a chemotherapy-induced premature senescence/aging model and xenograft transplantation mouse models, we have shown that the temporal dynamics of senescent cell turnover are distinct between females and males. Our data clearly indicated that females have advantages in eliminating senescent cells, potentially providing improved health.

With a proteomics approach, we have identified a profile of differentially expressed proteins to distinguish senescent female and male mouse dermal fibroblasts (MDFs). Based on the fold change and p-value, we identified the fatty acid binding protein FABP5 as a top hit, and decided to further study its role in mediating the sexual dimorphism in senescent cell turnover. Interestingly, knock-down (KD) of Fabp5 in male senescent MDFs made their immune clearance more efficient and these KD cells gained a gene expression profile that is more comparable to the female senescent cells.

In this project, using various cell culture models, we set to identify the function(s) of the target proteins that were affected by FABP5 KD in male cells and to explore the downstream mechanisms about how FABP5 mediates the sex disparity in senescent cells.

Experience from student: Hands-on experience with cell culture and molecular biology

Supervisor: prof. André Aleman MD PhD

Field of research: Cognitive Neuroscience

Description: Cognition is associated with daily functioning in elderly people, but inconsistent findings have been reported across studies regarding the precise nature of this association. This study aims to investigate cognitive predictors of independence in activities of daily living among community-dwelling older adults. A total of 187 Dutch participants aging from 51 to 92 years volunteered to the study. Their daily functioning was assessed using the Instrumental Activities of Daily Living scale and the Functional Activity Questionnaire, while multiple cognitive domains were measured using various neuropsychological tests (e.g., trail-making test, WAIS digit span, verbal fluency). The Geriatric Depression Scale was also included as a possible moderator variable. A specific question that will be addressed regards the role of executive functioning over and above other measures of cognition. MRI brain scans are available for a subset of participants. Related to this, the question can be addressed whether frontal cortex gray matter volume is associated with cognition and everyday functioning. Resting state connectivity of brain networks can also be investigated in relationship to cognitive measures.

Supervisor: prof. Martin H. de Borst MD PhD, Tamas Szili-Torok MD PhD

Field of research: Epidemiology 

Description: The global incidence chronic kidney disease (CKD) has been steadily rising in the recent years resulting in a growing population of kidney transplant recipients (KTR). Acute rejection in the KTR population is now infrequent, attributable to high quality immunosuppressive medication regimens. Therefore, clinical focus has shifted towards preventing chronic complications. One such complication is new onset diabetes after transplantation (NODAT), which affects up to 50% of KTR. NODAT is associated with worse patient and kidney allograft outcomes. NODAT onset is possibly preventable, however, KTR at risk need to be reliably identified. At this moment, there are no good risk prediction algorithms available. Therefore, during this project you will use nuclear magnetic resonance (NMR) spectra to try to identify KTR at NODAT risk. The NMR spectra is represented as ~27 000 columns in a database which includes ~700 KTR. Working with such high dimensional data will require you to use machine learning/data science techniques such as feature selection and dimensionality reduction to successfully complete the project.

Experience from student: background in one or more of the following topics: epidemiology, statistics, coding, and machine learning

Supervisor: prof. dr. Hélder A. Santos

Field of research: Biomedical technology & Immunotherapy

Description: The recent cutting-edge advances on nanomaterials are anticipated to overcome some of the therapeutic window and clinical applicability of many drug/peptide molecules and can also act as innovative theranostic platforms and tools for the clinic in the future. In the last decade, research on cancer and cardiovascular diseases resulted in a new set of potential treatments with promising results in the clinics, which culminated with the development of the first nanovaccines for COVID-19. Amongst the different experimental treatments, active cancer and immunotherapy, and targeted to the injured heart, hold great promise for the future treatment of these diseases. The students will be introduced to prominent nanosystems, such as biohybrid nanocomposites made of different nanoparticles and cell-based membrane extracts as potential platforms for the individualization of medical intervention and biomedical applications. Examples on how biohybrid nanomaterials can be prepared and tested for immunotherapy, as well as how they can be used to enhance the drug’s targetability, intracellular drug delivery for both cancer chemo- and immune-therapy applications as well as other applications, will be experienced.

Supervisor:  Prof. J. Marc C. van Dijk MD PhD, D.L.Marinus Oterdoom MD PhD

Field of research: Neurosurgery

Description: Deep brain stimulation (DBS) is a neurosurgical operation used for the treatment of various conditions, such as Parkinson’s Disease (PD) and Obsessive Compulsive Disorder (OCD). In DBS, electrodes connected to an Internal Pulse Generator, are placed inside the brain. Electrical pulses can then influence the way a certain brain area functions. Many patients are treated with this technique for a disease which would otherwise be unmanageable. The DBS-operation has been modified over the years. E.g: a few years ago the procedure in the Universitair Medisch Centrum Groningen (UMCG), was performed whilst the patient was awake, allowing the neurosurgeon to make sure that no essential parts of the brain are harmed during the procedure. Currently the procedure in the UMCG is to place the patient under general anesthesia whilst the operation is performed. Besides this difference in anesthesia use changes were made in surgical technique and hardware. Complications that may arise as a result of the surgery and the effects of the DBS itself, are relevant. The aim of this retrospective study is to determine the prevalence of various complications that arise as a result of DBS surgery. This will be done by analyzing a patient cohort database from the UMCG.

Supervisor: E.I Metting PhD

Field of research: Epidemiology

Description: Health organisation and the European union stimulates the development and implementation of digital healthcare by health programs and grants. Moreover, cross-border healthcare use can improve healthcare and accessibility. Collaboration between countries is needed to make this work. Unfortunately, there is nothing about go through differences regarding health, technology acceptance.

Aim of this study is to explore possible, cultural differences in health technology, acceptance of intern students.

Method: the unified theory of technology acceptance will be used as basis for the questionnaire. During the conference, we will place QR codes with the link to an online questionnaire in the UMCG. Students can scan the code and fill in this short online questionnaire. We will also collect the country of the students and some basic demographics. The results of the questionnaires will be compared with the characteristics of the different countries (Hofstede dimensions). The data will be analysed using R or SPSS. Descriptive and inferential analysis will be performed with ANOVA’s and T-tests or their non-parametric alternative.

Results: the students will provide an overview of the technology, acceptance rate per country/continents and looks for cultural factors related acceptance.

Supervisor: Yanyan Fu PhD (postdoc) & Girbe Buist (Associate professor)

Field of research: Medical Microbiology and Infection prevention/Molecular Bacteriology

Description: There is an urgent unmet need for reliable novel biomarkers for progression of chronic inflammatory disease and for therapy monitoring. Patient antibodies discriminating the wide chemical variety of bacterial peptidoglycans (PGN) represent a robust, new, and specific biomarker. PGN is an essential building block of the cell wall of all bacteria and has strong inflammatory actions. Since PGN peptide sequences differ between groups and individual species, we aim to develop methods for detection of PGN (fragments) in human samples. The various bonds in PGN can be cleaved using different types of PGN-hydrolases (PGHs). Depending on the specific cleavage sites, three main types of PGHs can be distinguished, including glycosidases, amidases, and endopeptidases (Wang, 2022). The general structure of PGN and predicted B-cell epitopes for antibodies are shown in the Figure. For Staphylococcus aureus, most of the biologically active PGHs have been isolated after heterologous production in Lactococcus lactis (Romero Pastrana, 2018).

Peptidoglycan will be isolated from different S. aureus strains and the concentration will be detected using fluorescently labeled Vancomycin. Through hydrolysis of purified PGN using different combinations of PGHs specificities, specific individual PGN fragments can be generated. PGN fragments are bound to membranes for dot-blot detection or to microtiter plates for ELISA approaches to determine quantitative responses of IgM, IgG or IgA against the various PGN fragments. Human sera will be used to determine the variation of natural responses against PGN fragments that are present in serum.