Guillermo Montoya

Guillermo Montoya says: “Genome editing is a technology that allows modification of the instructions contained in a genome and perhaps to “write” a new set of instructions to generate new genomes using the genetic code. This technology can be applied in therapeutics, especially in diseases where mutations produce illnesses and where a cell type is amenable for modification, such as for example bone marrow cells. Therefore, genome editing can be applied, to correct mutations causing rare diseases and certain types of cancer. To improve these applications, we need to get full mechanistic understanding of the “tools” that we use to initiate the modification. My proposal focuses in deciphering the working mechanisms of different CRISPR-Cas systems to provide better molecular scissors for various applications.”

Michael Lisby

Michael Lisby says: “Mutation of DNA helicases is responsible for a number of immunological disorders, infertility, neurodevelopmental defects, premature ageing syndromes and predisposition to cancer. We have discovered a new human helicase ZGRF1, which is important for repair of DNA lesions that block DNA replication. Replication-blocking DNA lesions are particularly toxic to cells, because they can lead to chromosome missegregation if not repaired before cell division. This is especially true for rapidly dividing cancer cells but also for cells undergoing rapid cell divisions during development and differentiation. With the proposed project, we will investigate the function and regulation of ZGRF1 and its implications for human health and disease to uncover its potential as a therapeutic target.”

Poul Nissen

Poul Nissen says: “The project is about solving structures of key receptors involved in nutrient uptake. A key system for control of our load of available sugar in blood stream versus deposition of energy resources is insulin and the insulin receptor. We will investigate how insulin activates the receptor to perform downstream control of other molecules and metabolic systems in the cell, and we will investigate its regulation in for example brain. Similarly, we will investigate a major amino acid (from protein in the diet) uptake system. Nutrient uptake is of key importance to all organisms and in humans it involves and controls numerous physiological processes and behaviour so that we seek food and eat properly without missing nutrients or overloading our system. Our studies will be highly enlightening for novel ideas and strategies in development of new medicine or procedures for treatment of metabolic disorders such as type 2 diabetes.”

Jens Bukh

Jens Bukh says: “A growing global health problem is antiviral resistance, which arises when viruses change (or evolve) to render drugs or vaccines ineffective. But how viruses develop antiviral resistance is poorly understood, and this limits our ability to combat infections and to develop compounds impervious to resistance development. We will use hepatitis C virus (HCV), which infects 71 million people and causes 400,000 annual deaths, as a model to study the mechanisms of antiviral resistance in unprecedented detail, as the inherent capacity of HCV to evolve and escape antiviral drug pressure remains a challenge. We will determine the key viral and cellular elements and molecules of resistance development, and how they interact to confer resistance. Thus, novel concepts pursued here will define how to prevent antiviral resistance in viral infections.”

Niels Mailand

Niels Mailand says: “Many chemotherapeutic agents give rise to the formation of DNA–protein crosslinks, a highly toxic form of damage to the genetic material within our cells. However, little is known about how human cells respond to and overcome such lesions. Using cutting-edge methods within cell and protein biology, this project will explore how the cellular response to DNA–protein crosslinks is organized and regulated at the molecular level and how targeted inhibition of such processes may be exploited in improving treatment strategies for cancer.”

Mikkel Heide Schierup

Mikkel Heide Schierup says: “Our sex chromosomes, the X and the Y, are mysterious. They influence male fertility and have a disproportional role in creating new species, including our own. I hypothesize that this is due to a tug-of-war between the X and Y for entering sperm cells in male meiosis. To test this, I will investigate all stages of human male meiosis using advanced cell sorting and sequencing and relate this to male fertility and the sex of children. I will include other great apes and archaic humans such as Neanderthals to understand the general evolutionary rules and the specific speciation processes as well as genetic causes for male infertility.”

Anders H. Lund

Anders H. Lund says: ”The ribosome is the key interpreter of genetic information in all living organisms. However, despite its pivotal role, very little is known about how the ribosome is regulated. The project explores the hypothesis that modifying the ribosomal RNA regulates ribosome function and impacts protein translation. Understanding how the ribosome is regulated to tune translation will provide better understanding of how gene expression programmes are faithfully executed and may provide insight on diseases in which translational control is pathologically hijacked.”

Søren Riis Paludan

Søren Riis Paludan says: ”In this project, we will explore how the first line of defence against infections is activated following virus infections. We will identify cellular and molecular mechanisms through which cells and tissues sense and respond to viruses. The project may uncover fundamentally new mechanisms through which the immune system mounts the first barrier against infection. This may impact the development of new antiviral therapy and is likely also to uncover mechanisms of importance for other conditions, such as non-viral infections and autoimmune diseases.”