High-resolution microscopy technology bypassing the diffraction limit - 26/10/2023

From micro- to nanoscope

It has long been impossible to distinguish objects closer than 200 nanometres using light microscopes. However, novel devices developed by a company called abberior Instruments GmbH, which use technology developed by Nobel Prize winner Prof. Dr. Stefan Hell and his teams in Heidelberg and Göttingen, are now able to bypass this resolution limit and provide detailed insights into living cells in the lower nanometre range.

Jun.-Prof. Dr. Priscilla Briquez, junior professor at the Department of General and Visceral Surgery at the Freiburg University Medical Center and member of the Medical Faculty at the University of Freiburg, has received a European Research Council (ERC) Starting Grant from the European Commission. Her DRESSCODE project will receive a total of 1.5 million euros funding for five years.

Epigenetically active drugs enable the cell to read parts of the genome that were previously blocked and inaccessible. This leads to the formation of new mRNA transcripts and also new proteins, as scientists from the German Cancer Research Center and the University Hospital Tübingen have now published. These "therapy-induced epitopes" could help the immune system recognize cancer cells.

Epigenetically active drugs enable the cell to read parts of the genome that were previously blocked and inaccessible. This leads to the formation of new mRNA transcripts and also new proteins, as scientists from the German Cancer Research Center and the University Hospital Tübingen have now published. These "therapy-induced epitopes" could help the immune system recognize cancer cells.

Why are severe courses of SARS-CoV-2 infection less common in children and adolescents than in adults? Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now discovered that the immune system in the upper respiratory tract is much more alert and active in children before infection than in adults and is therefore better equipped to fight the virus.

The development of highly specific T-cell engagers directed against pHLA tumor targets will be quick and easy. BioCopy's innovative pHLA screening technology characterizes drug candidates in great depth for their specific binding against the desired pHLA tumor target. YUMAB develops highly specific antibodies with their advanced antibody technologies.

A phase I clinical trial is now starting at Tuebingen University Hospital in the Clinical Collaboration Unit (CCU) Translational Immunology, in collaboration with the Department of Internal Medicine I, which is investigating the therapeutic cancer peptide vaccine Fusion-VAC-XS15 in combination with immune checkpoint blockade by atezolizumab (Tecentriq®).

Tumor vaccines can help the body fight cancer. These vaccines alert the patient's immune system to proteins that are harbouring cancer-typical alterations. Physicians and cancer researchers from Heidelberg and Mannheim have now treated adult patients with advanced midline gliomas, difficult-to-treat brain tumors, with a peptide vaccine for the first time.

The computational design of new proteins for biomedical or other applications involves long computing times on powerful servers. A joint team of researchers from the Max Planck Institute for Biology Tübingen and the University Hospital Tübingen has now developed and tested a new computational method to greatly speed up the necessary energy calculations. Their framework allows for a precise and efficient design of functional proteins.

DNA nanotechnology - 25/08/2023

Artificial cytoskeleton made of DNA for synthetic cells

The physicists Prof. Dr. Kerstin Göpfrich and Prof. Dr. Laura Na Liu want to understand life from the bottom up. They intend to do this by constructing an artificial cell. However, rather than natural protein building blocks, they are using 3D-DNA structures as construction material. The first step involved creating an artificial cell skeleton that dynamically assembles and disassembles like the biological model and can transport vesicles.

Known as the power plant of the cell, mitochondria are essential to human metabolism. Human mitochondria consist of 1,300 different proteins and two fatty biomembranes. The vast majority of mitochondrial proteins are produced with a cleavable transport signal and have to be actively transported into the mitochondria.

A new study published in Nature Medicine, July 2023 has identified two novel markers for screening high-grade squamous intraepithelial lesions (HSIL), a precursor to anal cancer, from the anal microbiome of people with HIV (PWH). PWH are at a significantly higher risk of developing anal cancer. Current screening methods, such as anal cytology, have low specificity for detecting HSIL, which hinders the prevention of anal cancer.

The function of mast cells, which are part of the immune system, is still a mystery. Scientists at the German Cancer Research Center (DKFZ) have now shown in mice: mast cells function as a sensor that signals the animals to avoid antigens, including harmful allergens, and thereby protect themselves from health-threatening inflammatory reactions. The findings were published in the journal Nature.

Researchers from Konstanz and Zurich have deciphered a biochemical mechanism that ensures that newly formed proteins are processed correctly when they leave the cell's own protein factories. This solves a decade-old puzzle in protein sorting.

Predicting the success of cancer treatment - 20/06/2023

Focusing on gut microbiome for CAR T-cell therapy

Cancer immunotherapies use the body's own defences to fight tumour cells. An international consortium of researchers from Germany and the USA led by the DKFZ in Heidelberg has demonstrated that the effectiveness of CAR T-cell therapies greatly depends on the composition of the gut microbiome. The researchers have also developed a model for predicting the long-term response to the treatment.

Impaired function of lung fibroblast is considered causative for symptoms of the incurable lung disease COPD (Chronic Obstructive Pulmonary Disease). Using high-resolution epigenetic profiling, German and British scientists have now identified potential targets for COPD treatment. The team detected early epigenetic changes in the genome of COPD fibroblasts, providing new insights into the disease pathogenesis and potential therapeutic avenues.

Volkswagen Foundation to fund international research project with around 1.5 million euros. Interdisciplinary team led by the Institute for Global Health at Heidelberg University Hospital to research the transmission of pathogens from animals to humans in Thailand and Laos. Long-term goal is to develop sustainable preventive measures against future pandemics.

Chronic myeloid leukemia (CML) is a type of blood cancer that arises from malignant changes in blood-forming cells of the bone marrow. It mainly occurs in older individuals and represents about 20 percent of all adult leukemia cases. A research team from the Institute of Molecular Medicine and Cell Research at the University of Freiburg has now demonstrated for the first time that mast cells play a crucial role in the development of CML.

Proteins have characteristic amino acid sequences, the analysis of which is fundamental for research and medicine. These can be decoded; however, so-called protein sequencing is expensive and time-consuming. A large-scale research project led by Prof. Dr. Jan Behrends from the Institute of Physiology at the University of Freiburg now aims to establish a new technology for protein sequencing using nanopores, which will be rapid and cost-effective.

Konstanz researchers discover the function of a previously unexplored protein: In three characteristic steps, "C12orf29" links the ends of RNA strands. Proteins that perform this kind of RNA ligation were previously unknown in humans. The results of the study suggest that it is important for RNA repair during cellular stress.

Heidelberg scientists succeed in boosting the efficiency of CRISPR/Cas9 and related methods and modifying initially inaccessible DNA sequences.

The hospital pathogen Pseudomonas aeruginosa requires the sugar-binding proteins LecA and LecB to form biofilms as well as to attach to and penetrate host cells. These so-called lectins are therefore suitable targets for active substances to combat Pseudomonas infections. Researchers from Saarbrücken and Freiburg have now produced potent inhibitors for LecA and LecB that are more stable and soluble than previous drug candidates.

Mitochondria are considered to be the power plants of cells and are essential for human metabolism. Dysfunction in 40 percent of mitochondrial proteins are associated with human diseases, which is why mitochondria also play an important role in medical research. A previously unexplained process in the complex mitochondria was the formation of their barrel pores.

In our bones, specialized cells called osteoblasts are responsible for building up bone substance. A team of researchers led by scientists from the DKFZ-Hector Cancer Institute at the University Medical Center Mannheim* and the University Medical Center Hamburg Eppendorf has now identified an enzyme that controls the activity of osteoblasts.

Inhibition of a protein complex in cells of the immune system prevents rejection of transplanted organs – this has been shown in a study by immunologists from the University of Konstanz, the Biotechnology Institute Thurgau (BITg) and Chongqing Cancer University Hospital.