During the annual AG&M meeting in Garderen Prof.dr. Chris Polman handed out the AG&M grants of 2017. Jelmi uit de Bos has been awarded with The AG&M international student research fellowship and Daniel Miedema has been enrolled in The AG&M PhD talent development program.
AG&M international student research fellowship
Jelmi uit de Bos
I am currently finishing the first year of the research Master Biomedical Sciences at the University of Amsterdam (UvA), specializing in Biochemistry and Metabolic Disease. A compulsory element of this program is to perform two internships at labs of your own choosing. For my second internship, I wanted to join the group of David Sabatini at the Whitehead Institute, as I believe this will be an ideal environment to optimally develop myself and prepare me for a career in research. I am therefore grateful for the opportunity the AG&M international student fellowship provided to perform an internship at this top-notch institute.
My interest in biomedical research was sparked soon after starting my studies, where I followed a wide variety of courses, on topics such as molecular biology, genetics, immunology and microbiology. During my study I participated in the research honors program, where I designed and executed my own research plan in the group of Dr. Riekelt Houtkooper at the Academic Medical Centre in Amsterdam. Here, I developed a growing interest in metabolism. Since the AG&M institute specializes in the field of metabolism and gastroenterology, the AG&M international student research fellowship provides a great opportunity to facilitate this key step in my career.
I will be performing my research in the group of Dr. David Sabatini starting in September. My research will focus on one-carbon (1C) metabolism, an essential pathway that is important for nucleotide synthesis, redox balance, and epigenetic maintenance. 1C metabolism is highly conserved throughout evolution and comprises a set of reactions that depend on the co-factor tetrahydrofolate (THF) to transfer 1C units to a diverse set of targets. 1C metabolism is compartmentalized between mitochondria and the cytosol and both compartments contain parallel pathways with isoenzymes present for each step. Despite its important role in metabolism and cell function, several aspects of 1C metabolism remain unknown. Therefore, I am going to study 1C metabolism using techniques recently developed in the Sabatini lab and ultimately hope to get a better understanding of the mechanisms underlying this complex metabolic pathway.
AG&M PhD talent development program
After a study in physics and specialization in biophysics during my PhD, I started working on oncology during my postdoc at the AMC. I find it very exciting to apply the quantitative approaches, which I have learned while working in physics, to study the growth mode and therapy resistance mechanisms of GI malignancies. The combination of wet-lab experiments and theoretical approaches within one group makes the Laboratory of Experimental Oncology (LEXOR) at the AG&M institute an excellent environment to study the tremendous problem of drug resistance in cancer treatment.
Carcinomas formed in the lining of the gastrointestinal (GI) tract are best treated surgically combined with adjuvant therapy. However, if the bulk of malignant cells cannot be surgically removed, e.g. in a metastatic setting, therapy alone has a limited ability to cure patients. It appears that, below toxic levels, chemotherapeutics, radiation and targeted therapy all have an insufficient efficacy to eradicate malignant cells, such that an initial positive response to (first line) therapy is frequently followed by tumor relapse by the outgrowth of a small fraction of resistant cells. In particular for targeted therapy, the strong heterogenic response of cells to treatment points to an underlying cause of a molecular heterogeneity in the population of malignant cells within a malignancy.
In this project we will study how intra-tumor heterogeneity arises during the transformation of healthy tissue into a malignancy using mathematical modeling. We will develop stochastic models to study the growth mode of solid malignancies. The evolutionary process of competing cells (or “clones”) determines the amount of molecular heterogeneity within a malignancy. Our models will predict whether competition between clones is neutral or dominated by a small fraction of fit clones. In close collaboration with wet-lab experimentalist, we will apply model predictions to quantitative experimental data to arrive at a better understanding of the molecular heterogeneity in tumors. The ultimate goals here are to unravel the evolutionary processes underlying oncogenic development and understand how resistance to therapy arises.