Three KI researchers named Ragnar Söderberg Fellows 2016
Three young researchers at Karolinska Institutet have been awarded the Ragnar Söderberg Fellowship in Medicine for 2016, and are each to receive a research grant of SEK 8 million over five years. The three awardees are Magda Bienko, Nicola Crosetto and Simon Elsässer, all also affiliated to at SciLifeLab.
The Ragnar Söderberg Fellowship in Medicine is awarded to promising young researchers at the start of their careers to help them establish innovative research environments and develop as independent scientists. This year, five researchers have been awarded grants, three of whom are group leaders at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics (MBB).
Spatial organisation of the genome in breast cancer
Fellow: Magda Bienko, Assistant Professor, MBB
Most human cancers contain alterations in the number and structure of chromosomes that are associated with poor prognosis. In breast cancer chromosomal alterations represent a major mutation type that causes deregulated expression of many genes, which in turn can fuel tumor progression. Independently of the type of alteration, chromosomal rearrangements will exert a global effect on the architecture of the genome, which in turn will affect global gene expression profiles. To fully understand the pathologic consequences of chromosomal alterations, a thorough picture of the 3D structure of rearranged cancer genomes is needed.
Using state-of-the-art methods of sequencing and microscopy, Magda Bienko studies how structural chromosome changes affect the spatial organisation of the entire genome with the aim of building a catalogue of the different chromosome changes and focusing on local topologies in the most commonly occurring breast cancer genes. Thanks to the laboratory’s unique microscopy tools, she is able to pick out structural details direct in the cells and monitor their activity.
The objective of Magda Bienko’s project is to understand the principles for how the genome adapts to the dramatic structural changes that occur in breast cancer. Potentially, she will be able to discover new universal weaknesses in cancer cells that can lead to new treatment strategies.
Advanced determination of cellular variation in a tumour
Follow: Nicola Crosetto, Assistant Professor, MBB
For the past few decades, many leading cancer centres around the world have started developing therapy programmes based on the concept of personalised cancer medicine instead of treating all cancers as the same. However, despite huge investments in the field, many such targeted treatments fail, probably because the individual tumour comprises its own highly complex ecosystem consisting of millions of cells with different properties.
This variation, referred to as intra-tumour heterogeneity” (ITH), goes a long way to determining how, and even if the tumour will respond to treatment, and if it will generate life-threatening metastases. New, reliable methods need to be developed that can measure and visualise ITH, and then convert the information into something doctors can use.
Nicola Crosetto is taking up this challenge by developing advanced techniques and algorithms for measuring different parameters in cancer samples and using them to chart ITH in breast cancer patients treated with neoadjuvant chemotherapy prior to surgery. The project uniquely integrates the state-of-the-art technology being developed at the Science for Life Lab with clinical expertise from Karolinska University Hospital, helping to place Sweden at the cutting edge of personalised cancer therapy.
The relevance of short peptides coded by sORFs
Fellow: Simon Elsässer, Assistant Professor, MBB
Cells are teeming with short peptides (sPEPs) translated by short open reading frames (sORFs). However, despite their abundance, their function remains a mystery. Recent analyses of the entire genome and mass-spectrometry studies have shown that there are over a thousand different sPEPs in mammalian cells. Studies of a handful of sPEPs reveal that many of them are involved in human biology and relatable to disease.
The aim of Simon Elsässer’s project is to systematically identify and name the short peptides coded by sORFs, and determine their place in the cell, their peptide stability and their molecular function.
The project is the first of its kind: no previous study has been set up to understand the function of the myriad human sPEPs and to identify potential biomarkers and peptides for drugs to act against.
Swedish text (here in translation) and photo: The Ragnar Söderberg Foundation
View a film from the Ragnar Söderberg Foundation