Both current Digital Life Norway projects and members of the centre's expert task force are involved in new projects.
New project in precision cancer medicine from matchmaking facilitated by the centre
Last fall DLN teamed up with the Swedish SciLifeLab to match PhDs and postdocs associated with DLN through research projects or the research school with research groups at the Swedish SciLifeLab. The aim was for them to apply for three-year researcher projects with international mobility. As a result of this matchmaking process Christa Ringers at the Kavli Institute for Systems Neuroscience at NTNU was granted 3,9 MNOK for the project "Phenotypic Drug Screening to support personalized medicine for colorectal cancer". She will share her time between research groups at SciLifeLab and Uppsala University and the research group of Åsmund Flobak and Astrid Lægreid who are PIs of the DLN projects DrugLogics and PRESORT at NTNU.
Popular science summary
Every cancer patient poses a distinctive challenge to physicians. Colorectal cancer is not one but rather a collection of similar diseases of abnormal tissue growth in the colon. Due to the variable underlying disease biology, tumours targeted by a drug may respond well to the treatment in one person but not in the other.
Certain strategies have emerged to match a person with their optimal drug, probing the unique disease biology of their cancer and tailoring the treatment to their individual needs – an effort called personalized medicine. Approaches involving genetic screening are invaluable in specific cases, yet not mature enough to help most patients. This project proposes a novel personalized medicine strategy.
In our approach, a sample is derived from the patient’s tumour and nurtured into clumps of cancer cells – spheroids. By selecting targeted drugs that affect their growth and survival, physicians are provided with valuable information on possible drug responses. However, the information collected from these spheroids is limited.
To elaborately characterize cells, we will adopt a promising technique from the field of phenotypic drug screening. Cell Painting can characterize cells down to the organelle level - by using an optimized mixture of dyes - and so provide an abundance of information about the single-cell responses. In combination with current machine learning technology, the vast amount of data can be categorized and boiled down to important drug responses.
We aim to implement the Cell Painting technique into an existing personalized medicine pipeline, hopefully allowing for the identification of potential resistance mechanisms, and variability between patients. This project aspires to reveal the effect of drug treatments on various cancer cell types while gaining invaluable insight into the biological processes underlying tumour variability. Ultimately, our contributions have the potential to improve future cancer treatment responses and survival.
Funding for initial launch phase of the gigantic Earth BioGenome Norway initiative
The global non-profit initiative Earth BioGenome Project (EBP) is a moonshot for biology that aims to sequence, catalog and characterize the genomes of all of Earth’s eukaryotic biodiversity over a period of ten years. The grand vision is to create a new foundation for biology to drive solutions for preserving biodiversity and sustaining human societies. Kjetill S. Jakobsen, UiO, who is member of the DLN expert task force is leader of Earth Biogenome Project Norway (EBP-Nor). UiO, NMBU, UiB, NTNU, Uni Nord, UiT, SINTEF, REV Ocean, the Life Science Cluster, the Norwegian Environment Agency, and ArcticZymes Technologies are partners in the project. Together they will sequence and catalogue all eukaryotic species occurring in Norway, estimated to 45,000 species. The initiative was granted 30 MNOK for the project "A Norwegian BioGenome initiative: the initial Launch phase" from the call Collaborative Project to meet Societal and Industry-related Challenges.
Popular science summary
Biodiversity is increasingly threatened by human-related activities, directly and indirectly, which ultimately imperils both the global food supply and other biological resources that we depend upon. Therefore, understanding and preserving species and ecosystems are global imperatives for human survival and prosperity. Each organism and species on the planet has a unique "blueprint" encoded by its genome, i.e. its total DNA, which contains all the information that the species needs to survive, interact with its environment and reproduce. Knowing and understanding the complete DNA sequence of all species of life on Earth will not only provide fundamental new insights into biology, understanding biodiversity and transform our ability to tailor conservation of life, but also deliver a comprehensive view of nature’s toolkit for future biotechnology to provide humanity with food, medical treatment, drugs, vaccines, biofuels and biomaterials. The Earth BioGenome Project is a global non-profit initiative that aims to sequence and catalogue the genomes of all of Earth's 1.5 million currently described eukaryotic species over a period of ten years. EBP-Nor is the Norwegian initiative of EBP, and a partnership of the major universities in Norway (UiO, NMBU, UiB, NTNU, Uni Nord and UiT), the research institute SINTEF, and the non-academic institutions REVOcean, the Life Science Cluster, the Norwegian Environment Agency, and ArcticZymes Technologies. Together we will sequence and catalogue all eukaryotic species occurring in Norway, estimated to 45,000 species.
Several other projects for researchers affiliated with the centre
Nanoscale artificial intelligence in microscopy and nanoscopy for life sciences (*NanoAI)
Krishna Agarwal and Balpreet Singh Ahluwalia, UiT in the DLN project nanoRIP are partners in the project lead by Dilip K. Prasad, UiT.
Researcher Project for Scientific Renewal, Ground-breaking Research (FRIPRO), 12 MNOK
Summary
*NanoAI will develop new frameworks of interpretable and analyzable artificial intelligence (AI) designed specifically for microscopy and nanoscopy so that microscopes and nanoscopes can be transformed from a visualization device to a powerful knowledge discovery tool. Within the *NanoAI project duration, AI solutions for both tissues and living cells will be developed and tested on cardiac tissues and living cardiac cells as a proof-of-concept. The project will start from October 2021 under the leadership of Assoc. Prof. Dilip K. Prasad (Department of Computer Science, UiT), together with partnership of Prof. Balpreet Singh Ahluwalia and Assoc. Krishna Agarwal from the Nanoscopy group (Department of Physics and Technology) and Assoc. Prof. Åsa Birna Birgisdottir (Department of clinical medicine, UiT).
Unlocking the potential of precision medicine to promote drug sensitivity in lung cancer
Dagim Tadele, OUS in the DLN project PINpOINT
Three-year Researcher Project with International Mobility, Ground-breaking Research (FRIPRO), 3,7 MNOK
Animal Model for evaluation of Innovative immunotherapy DEsigns – (AMIDE)
Emmet McCormack, UiB, in the DLN project CCBIO
Researcher Project for Scientific Renewal, Ground-breaking Research (FRIPRO), 12 MNOK
Deciphering Heterogeneity to provide treatment for metastatic Endometrial cancers
Camilla Krakstad, UiB, in the DLN project CCBIO and member of the DLN expert task force
Researcher Project for Scientific Renewal, Ground-breaking Research (FRIPRO), 11 MNOK
Markov State Models for Cellular Phenotype Switching
Susanna Röblitz, UiB, member of the DLN expert task force
Researcher Project for Scientific Renewal Ground-breaking Research (FRIPRO), 7 MNOK
Popular science summary
This project aims at identifying the dynamics of cellular phenotype switching from stochastic gene regulatory networks. Models for cellular phenotype switching enhance our mechanistic understanding of cell fate decisions, cellular differentiation processes and reprogramming, thus providing insight into, for example, tumor progression and cancer. Nearly every cell in a person's body has the same DNA. However, thanks to gene regulation, each cell expresses (“turns on”) only a fraction of its genes at any given time. These different patterns of gene expression cause various cell types to have different sets of proteins, making each cell type uniquely specialized to do its job. In addition, gene expression is a fundamentally stochastic process. Randomness in transcription and translation leads to significant cell-to-cell variations in mRNA and protein levels, with important consequences for cellular function. Stochastic changes in particular patterns of gene expression can lead to spontaneous phenotype transitions (“switches”), being beneficial in some contexts and harmful in others. Stochastic gene regulatory networks can be modeled mathematically in terms of Markov jump processes and the Chemical Master Equation (CME). Given such a network model, we are interested in the number and characteristics of different phenotypes as well as in the transition probabilities and pathways between them. These numbers can be approximated from the CME by a projection method called Markov State Modelling. In this project, we want to overcome the current limitations of this method by developing new numerical algorithms and software tools that allow us to construct Markov State Models with quantified accuracy for high-dimensional stochastic gene-regulatory networks. We will demonstrate the relevance of Markov state modeling for understanding cellular phenotype switching by applying the algorithm to models for macrophage polarization, T-cell and stem cell differentiation.
CellFit: T cells fit to fight cancer
Hanne Haslene-Hox, SINTEF, member of the DLN expert task force is a partner in the project lead by Else Marit Inderberg, Oslo University Hospital, Radiumhospitalet, 23 MNOK
Summary
CellFit: T cells fit to fight cancer Clinical outcomes reported for solid tumour adoptive cell therapy have been disappointing compared to liquid cancers. To improve therapeutic efficacy and treatment cost-effectiveness which depend on long-term clinical outcome, T-cell manufacturing methods require development. Standard, non-optimal, formulae are currently used in manufacture and a great knowledge gap exists for which factors are required to produce clinically optimal T cells in an artificial in vitro expansion versus a successful physiological in vivo T cell response. Large-scale testing is required to identify these factors. By merging automated high-throughput screening technologies with clinical T-cell manufacturing and the access to innovative reagents we will provide significantly improved cellular products (more active and in vivo persistent) and processes (higher yields, more streamlined). Although high-throughput screening approaches are used to identify and select targets or antigens in T-cell therapy, no one is currently using these techniques to screen culture conditions to advance the T-cell manufacturing process. Developed screening systems will enable rapid evaluation of ex vivo T-cell efficacy by direct testing of 2D and 3D tumour-cell killing, T-cell phenotype and metabolism. T-cell therapy can be combined with e.g. checkpoint inhibitors or metabolic drugs in this screening to enable identification of useful treatment combinations for patient groups or single patients in a personalized medicine approach. The combined competencies of SINTEF and Oslo University Hospital, and Thermo Fisher within high-throughput screening, cellular therapy production and novel reagents will provide innovative new screening methods, improved cellular products and processes readily translated to improve clinical therapy and outcome. In collaboration with Oslo Cancer Cluster we will ensure public outreach and knowledge-sharing to foster responsible research and innovation.
Procedure for how to join the centre with new projects in pipeline
The discussion on how to secure recruitment of new projects to the Centre for Digital Life Norway (DLN) has been ongoing the last year as the first DLN projects are gradually coming to an end. The RCN has specifically encouraged projects that received support from the Collaborative Project to meet Societal and Industry-related Challenges, and that are relevant to DLN, to join the centre. Projects from other calls might also be relevant. The upcoming calls from the RCN on technology convergence linked to enabling technologies for research projects; and collaborative and knowledge-building projects is another opportunity.
Projects affiliated with DLN have access to guidance and support within data management, cross-disciplinary and cross-projects activities, innovation, industry collaboration and responsible research and innovation (RRI) and communications.
The centre is preparing procedures for how new projects, like the newly funded projects mentioned in this article, may apply to join the centre and become part of the Digital Life Norway portfolio. Information about this will be announced on our webpage and our newsletter this fall.