The Beyond 1 Million Genomes plus (B1MGplus) project helps build a European cross-border network of genomic and clinical data to improve healthcare outcomes.

The project provides coordination and support to the 1+ Million Genomes (1+MG) initiative, a commitment by 25 EU countries and Norway to enable secure access to genomic and clinical data across Europe, supporting research, health policy and personalised healthcare.

The goal of the project is to identify NPC1/2-dependent specific protein/lipid alterations that modulate membrane tension along the endocytic pathway and, thus, endosome biogenesis.

NME6 belongs to the nucleoside diphosphate kinase (NDPK/NME/Nm23) family of enzymes that catalyze the transfer of the terminal phosphate from nucleoside triphosphates, to nucleoside diphosphates. During recent years, research revealed a growing number of NDPK/NME molecular functions related to human pathologies. The family consists of ten members divided in two groups. Group I members, NME1-NME4, are highly homologous among themselves and with orthologues in other Metazoans. They possess the NDPK activity in the hexameric form. The evolutionary older NME5-NME9 (Group II), display lower mutual homology and remain scarcely studied. Our group provided important information on NME6, an unusual NDP kinase and resolved existing discrepancies. We positioned the NME6 in the mitochondrial matrix, despite the absence of a canonical mitochondrial targeting sequence. Contrary to Group I members, NME6 prefers the monomeric state therefore lacking the NDP kinase activity. Physical interaction was confirmed with RCC1L (WBSCR16), a protein involved in mitoribosome assembly and translation. The overexpression of NME6 reduced the mitochondrial respiration capacity. Thus, our research revealed unexpected properties of NME6 and the NME Group II proteins, and opened new, important research avenues. In this project we will use standard and state-of-the art methods to 1) describe the non-canonical import of NME6 to mitochondria, 2) define its functioning hub within the mitochondrial protein expression, 3) provide biophysical answers to its oligomeric state and enzymatic activity and 4) explore interaction interfaces with its protein partners. We are confident that our research will not only answer questions about the biology of the NDPK/NME family but contribute to the understanding of the non-canonical mitochondrial import in general, the control of oxidative phosphorylation and the mechanisms of maturation of mitochondrial RNA and mitoribosome assembly, which remains poorly understood.

Uspostava istraživačke infrastrukture za translacijsku medicinu i primjenjenu genomiku s ciljem korištenja visoko-propusnih metoda temeljena na DNA čip tehnologiji za buduće aktivnosti tehnološkog transfera

The largest infrastructure project with the highest budget in natural sciences ever to be conducted in Croatia will foster a research pipeline at the RBI and facilitate innovation and technology for the investigation of relevant diseases such as cancer.

Although variants of uncertain significance (VUS) cannot be clearly defined and classified, VUS make up about 40% of the total variants in human, and their impact on the function or health of the organism is not known. It is necessary to implement a new and systematic experimental approach for the characterization of VUS at high throughput, and to contribute to the reduction of the amount of VUS in the relevant databases for a better understanding of genomic variation in humans.

EASIGEN-DS is about the establishment of a distributed European Research Infrastructure (RI) on Advanced Genomics Technologies. The project aims to become a world-leading research infrastructure in genomics, which is fully integrated into the European landscape. The project is expected to strengthen European capacity in sequencing technology, with a particular focus on third-generation sequencing offering longer reads and the ability to sequence without the need for amplification, and on single cell genomics and spatial transcriptomics.

The GoE project will create the first large-scale repository of genomic and phenotypic data in Europe, filling an important existing gap and removing dependence from non-European repositories for research and clinical applications. At the same time, it will also improve competitiveness by building key expertise and facilities for large-scale genomic analyses paving the way for additional data collection in the future. This project will bring Europe in line with similar ongoing projects in other countries including the US, China and Qatar. The benefits for society include applications in personalised medicine as well as the development of intellectual property in the EU based on complex large-scale genome data.