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The ISBGroup Blog

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Here you can read about everything that's happening in the ISB Group.

Double jackpot from Swedish Research Council – glowing 3R project reviews

Uncategorised Posted on Tue, November 07, 2023 02:25:35

This year, we got a double jackpot from the Swedish Research Council – who gave us glowing reviews for the 3R project, scaling from microphysiological in vitro systems to humans using scalable digital twins.

In Sweden, the Swedish Research Council (Swe: Vetenskapsrådet, VR), is the most central research grant, and it is often considered a key quality stamp of a top researcher to have at least one grant from VR. Therefore, competition is usually fierce (acceptance rate usually is 5-15%), and it is not at all guaranteed that you get money, even if you have a competitive application. Therefore, I am proud to say that this year, I got not only one grant, but two – and that the evaluation from the reviewers was unusually high and glowing.

The project I have gotten the review responses for so far is a special call on 3R, i.e. Replacement, Reduction and Refinement of animal experiments. This is a topic, I have been very active in ever since 2015, when I was awarded the first edition of the prize “Nytänkaren” (the thinker of new ideas), by the Swedish Fund for Research without Animal Experiments. The project extends on our experimental work, both within the group, doing cell biology cultures using 13C-labelled metabolites on liver and adipose tissue taken from surgery), and that in collaboration with AstraZeneca, centered around organs-on-a-chip, i.e. small microphysiological systems (MPS), with organoids and spheroids consisting of human cells (Fig A, recent paper). In the project, we will i) analyse these in vitro data using mechanistic modelling to get more information out of the data (e.g. metabolic fluxes), ii) plan new experiments, by first doing the experiments in the computer, and iii) translate the results to humans, by e.g. scaling the volumes of the spheroids to human sizes, and by adding the missing organs, which allows us to re-assemble the digital twin in the computer (Fig B-C, Step 1 and 2). The project will evaluate and quantify the benefits of this for e.g. drug development, and we will disseminate the results to pharma, scientists, and regulatory agencies (Fig C, Step 3).

In the evaluation, we only got 6s and 7s, which means that we were among the highest rated of all applicants, even among the few who got money (6 out of 56). The ranking is from 1-7, where a “normal, decent” scientist usually get a 3 (meaning “good”), and where you need at least a mixture of 5s and 6s to have any chance of getting money. If you get all 6s, you are usually getting the money for sure, and 7 is only very rarely given out (I was a reviewer for ~60 applicants two years ago, and then I think only one or possibly two got a 7 on any criterion). Therefore, I am very grateful that this year, I got only 6s and higher, and that two(!) categories got a 7: “merits of applicant” and “relevance for 3R” (Fig D). If the rating levels were the same as when I was a reviewer, I would – I think – have been number one of all applicants that year, and in any case, I must have been among the very top of all the 56 applicants also this year.

The life of a scientist is filled with many many rejected applications, so when you get a jackpot once in a while, it is important to stop a bit – and celebrate! Because tomorrow, it is time to get started working on the new exciting research projects! 🙂

Concluding keynote at Data-driven mechanistic modelling in life sciences

Uncategorised Posted on Mon, October 30, 2023 17:00:09

Last week, I had the honor of giving the concluding keynote lecture at the event “Data-driven mechanistic modelling in life sciences”. This follows a trend of being invited to give more and more keynote and plenary lectures at events, for which I am very grateful. Such longer lectures also give me the chance to expand a little bit more on my point-of-view. The focus of this particular workshop is also something I am very keen to promote, since I think that this particular overlap (mechanistic and data-driven modelling) is under-represented in many communities and conferences.

The centrality of this overlap is actually seen even in our group logo (Fig A). a) The fact that it has an open non-black box, represents the fact that we do mechanistic modelling. b) The data-driven aspect of our models is represent by the purple core in the middle, which represents the fact that we always look for core predictions. Core predictions are predictions that are well-determined from the current prior knowledge and data, even when taking all uncertainties in data and prior knowledge into account.

While I personally think that this is the way to work, and while we have a very well-established workflow for how to develop models in this fashion, mechanistic modelling and data-driven modelling are unfortunately often done in two disjoint communities, with too little overlap (Fig B). Mechanistic modelling often results in mere simulation-based results, which have not been validated using independent data, i.e. data that has not been used to train the model. This is often the case for e.g. PDE and agent-based models, but also common in e.g. theoretical ecology, theoretical biology, etc. It was therefore encouraging too see that one of the presentations at the workshop (by Joshua Bull) looked at spatial models, and on how to quantify the comparison between simulations and data also for spatial models. Data-driven modelling is too often interpreted to mean only machine-learning, narrow AI, and other black-box modelling techniques. While these are big and very hyped communities and approaches at the moment, they are not the only techniques that can be used to do data-driven modelling. In other words, while these black-box models include important techniques, which are useful if one has standardized large-scale data, they also have critical short-comings. Black-box models e.g. have big problems incorporating the type of data that is present in most biological papers, including the prior that is knowledge available. For these reasons, explainability and trustworthiness are challenges. I therefore think that hybrid modelling is the way forward (see e.g. this review, and this example). At the conference, there was also an excellent opening keynote of day 2, by Alvaro Köhn-Luque, which showed some additional and interesting examples of hybrid models.

Exceptional Half-Time Seminars: Meet Christian, Tilda, and Nicolas and Dive into Their Intriguing Research

Uncategorised Posted on Mon, May 08, 2023 08:14:00

Christian Simonsson

Titel: Mathematical modelling of diffuse liver disease

Opponents: Jan Boren and Matthias König

Date: 2023-03-01

Abstract: Christian has worked on constructing mathematical models in the context of NAFLD treatment and disease progression. One project has been focusing on creating a minimal mathematical model capable of simulating different dietary interventions, such low carb high fat diet (LCHF), and high fructose (HC) diets. To better understand treatment connection to changes in lipid fluxes. The second project has focused on determining liver function before hepatectomy, which is the only treatment option for HCC and liver metastasis. The two different projects have focused on each end of the NAFLD disease spectra, and the coming project will focus on modelling of non-alcoholic steatohepatitis (NASH)

Tilda Herrgårdh 

Titel: Hybrid modelling for diabetes and stroke prevention

Opponents: Maria Kjellsson, Anna Nordström

Date: 2023-03-02

Abstract: The long-term goal that the thesis will be a part of is to have a tool for prevention of metabolic and cardiovascular diseases, particularly stroke and its common precursor diabetes.  The plan is to use a digital twin and hybrid modelling. A digital twin can be used to make personalized predictions for different scenarios – lifestyle changes, diets, drugs, etc. – that can then be evaluated and compared. These predictions can include the long-term dynamics of different risk factors relevant for cardiovascular disease, such as BMI or fasting plasma glucose, or short term dynamics such as meal response glucose. These predictions can for example be used to understand the dynamics behind disease progression and to get continuous updated on progress of the changes made in real life, which can hopefully increase medical pedagogics and motivation. The long-term predictions of risk factors can be used in a hybrid modelling scheme as input in a machine learning model to get your risk score for having a stroke within a certain time span. The thesis covers the first steps towards, and a first example of the idea described above, as well as the development of models describing some of the different mechanisms relevant to diabetes and stroke progressions that can later be used in a comprehensive model of the entire progression. 

Nicolas Sundqvist

Titel: Systems modelling of human metabolism: Methods for 13C metabolic flux analysis and applications to the brain

Opponents: Elizabeth Klint, Dr. Katharina Nöh, Dr. Joao Duart

Date: 2023-01-17

Abstract: Nicolas has worked on constructing a mathematical model that can explain the mechanism that regulate the metabolism in the brain. This mathematical model explains what the cerebral metabolic response looks like in response neuronal activity induced by a visual stimulus. Furthermore, the work also includes how these mechanisms for the metabolic response connect to the mechanisms that of the neurovascular coupling. This work has resulted in a manuscript recently accepted for publication and will formed a base for future modelling endeavours. Additionally, Nicolas has worked with modelling intracellular metabolic fluxes using measurements of 13C isotope labels. A lot of this work have gone into method development for modelling stoichiometric models for 13C metabolic flux analysis (MFA) and has resulted in a publication where we present a method for validating such models when there is an uncertainty with respect to experimental measurement uncertainty. The plan for the continued work of Nicolas’ doctoral studies is to apply the methodologies for 13C MFA to a system for studying neurodegenerative diseases in neurological cell lines. As well as to investigate the mechanisms of the regulation of oxygen metabolism with respect to activity in different types of neuronal cells. 

CompBioMed Conference 2023: Munich, 12-14 September

Uncategorised Posted on Tue, April 11, 2023 08:58:00

CompBioMed Conference 2023 (CBMC23) will address all aspects of computational biomedicine, from genome through organ to whole human and population levels, embracing data driven, mechanistic modelling and simulation, machine learning and combinations thereof. This year Gunnar will is one of the Plenary Speakers and he will discuss physiologically based digital twins: a digital and interactive copy of yourself that follows you throughout your health journey.

You can read more about it HERE

Keynote lecture at the 7th VPH Summer School – Barcelona, June 5-9, 2023

Uncategorised Posted on Tue, April 04, 2023 07:33:00

Join the VPH (Virtual Physiologocal Human) summer school in Barcelona, June 5-9, 2023. This summer school includes 15 morning lectures, one honorary VPH lecture, and a lot of networking opportunities. Gunnar will talk about about the digital twins, so don’t miss it!

Last day to register is 21 of May, and you find more information HERE

M4-health and digital twins: bring a digital copy of yourself with you throughout your health journey 

Keynote Lecture, Wednesday June 7th, 2023, 09:30-11:00

Abstract: For the last 20 years, Cedersund has developed mechanistic mathematical models for all of the main organs in the human body: heart, liver, fat, brain, etc. Lately, these models have combined into an interconnected model for the body as a whole. This interconnected model can be made specifically for each individual, and is then called a digital twin. This digital twin technology employs a hybrid approach, which combines the mechanistic simulation models with machine learning and bioinformatics models. This allows a patient, doctor, or other end-user to look inside the body of a patient, as it is now, ranging from the whole-body to the intracellular level. This also allows for simulations of different future scenarios, ranging from ms to years, and can simulate e.g. the risk of a stroke, depending on choice of diets, exercise, and certain medications. The models are thus of an M4-nature: multi-level, multi-timescale, mechanistic, and multi-organ. The focus on this talk will be on how we systematically test mechanistically hypothesis on the intracellular and organ levels, using mechanistic modelling, optimization, and predictions with uncertainty – followed by corresponding model-designed experiments. I will also to some extent go through how we assemble the different organ sub-models together into the integrated digital twin, which in itself is a modelling problem, and how we then put all of this into a series of different eHealth apps.

BiosketcheGunnar Cedersund ( heads a cross-disciplinary research group at the Department of Biomedical Engineering (IMT) at Linköping University. The heart of this group (15+ people) does hybrid mathematical modelling, combining machine learning with mechanistic small- and large-scale models. These models are developed using both pre-clinical and experimental data of various types, which are collected both by experimentalists and clininicians within the same group, and by numerous collaborators. These models are made available for preventive and patient-centric care, as well as for drug development and medical pedagogics, using innovative eHealth technologies. This is made possible, e.g., via the fact that Cedersund heads the 6MEuro EU project STRATIF-AI, which brings his digital twins into healthcare for all phases of stroke (prevention, acute treatment, and rehabilitation), using a series of different apps, which all are connected to the same backend.

Digital twins to be tested in real health care environments

Uncategorised Posted on Mon, March 27, 2023 09:19:48

Digital twins will now be tested in real health care environments, in an EU-financed project. Gunnar is the project manager of STRATIF-AI, which has been granted SEK 65 million over a four-year period by Europe Horizon (the European Commission). The project is linked to stroke research, but the digital twins method is expected to have many different applications.

Read more about the project HERE

BME@LiU 2023 – Register Now

Uncategorised Posted on Mon, March 20, 2023 07:00:00

BME@LiU 2023 is a conference day filled with activities to highlight the research conducted at Linköping University (LiU) in the field of biomedical engineering (BME).

Biomedical Engineering, or MedTech, lies at the intersection of many of LiUs strength and strategic areas. It involves development of state-of-the-art technologies such as biosensors, medical imaging, AI, eHealth, visualization, with many applications in Life Sciences, e.g. circulatory and metabolic diseases, inflammation, neurological diseases and cancer.

BME@LiU is a day filled with activities related to the field of biomedical engineering. From invited and contributed talks, to posters, exhibitions, and mingling. These activities reach out to all researchers, companies, organizations, students and clinicians who support, contribute to, or utilize BME technologies.

If you would like to have an oral presentation, submit abstracts before March 27

BME@LiU 2023

When: April 20, 08.30 – 17.00

Where: Norra Entrén, Campus US and via Zoom

Read more and register here

Sign up: Workshop on Modelling in Biology and Medicine (MBM 2023)

Uncategorised Posted on Tue, March 07, 2023 13:39:24

Welcome to MBM 2023!  

We are pleased to invite you to our fourth Workshop on Modelling in Biology and Medicine (MBM 2023) on the 15-17th of May.  We aim to gather all young researchers in Sweden working on modelling of biological systems. Our ambition is to give all participating PhD students and Postdocs the opportunity to present their work through an oral presentation or a poster. Further, we wish to provide an insight into how modelling in biology and medicine is practiced in academia and industry.  

The workshop will be held in both plenary presentation sessions for larger talks as well as in smaller sessions for e.g. poster presentations. You can participate at MBM 2023 by  

  • giving a plenary talk,  
  • presenting a poster   
  • or simply as an observer  

The workshop will be in-person at Linköping University, Campus US. 

When: 15-17th of May 2023  
Where: Linköping 

Why: Bringing together young researchers in Sweden working on the border of mathematics, biology, and medicine  

How: Oral presentation, poster, or as an observer  
Abstract submission:, deadline 14th of April 
Register: Registration will open soon 

More information   

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