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Yu-Wen Chen

About Yu-Wen Chen is a first-year PhD student in the Interactive Intelligence group at TU Delft, supervised by Dr. Pradeep Murukannaiah and Prof. Dr. Catholijn Jonker. Prior to the start of this PhD position in September 2021, She obtained cum laude MA and MSc in Language and Communication Technologies from the University of Groningen and Saarland University. Her research focuses on using Natural Language Processing to recognize actors, values, and appeal within the climate change debate. Her project is part of the HIPPO DAI Lab , with the goal to support stakeholders with AI during the public policy deliberation and negotiation. Yu-Wen Chen Y.W.Chen@tudelft.nl Van Mourik Broekmanweg 6 2628 XE Delft The Netherlands

Meet & Eat | Local Community Engagement in Design Education – Can Cats and Dogs Live Under One Roof? with Reinout Kleinhans | 12 April

Meet & Eat | Local Community Engagement in Design Education – Can Cats and Dogs Live Under One Roof? with Reinout Kleinhans | 12 April 12 April 2022 12:30 till 13:30 - Location: Teaching Lab - By: Teaching Academy About this event | Click here to sign up directly Many lecturers at TU Delft seek to connect their teaching to current societal and global challenges in the ‘real’ world. This can require various forms of interaction with target groups, communities of ‘users’ or other stakeholders of design products. This is also known as community engagement. Think for example about the redesign of a neighbourhood park, a square or a public transport facility. However, community engagement (CE) is notoriously difficult in the context of time-bounded courses at TU Delft. While CE can have major benefits, real people and their interests can be harmed if students and their instructors mess up. Mutual Trust and reciprocity are delicate issues. So how to start if you want to incorporate CE in your teaching? In this Meat &Eat session, Reinout Kleinhans (Education Fellow 2020) will discuss the balancing act of engaging local (residential) communities and other stakeholders in student research in university courses. Underlying the short presentation is a conceptual framework that identifies six key challenges and practical solutions for CE in existing or new courses. This Meat &Eat session is particularly relevant for university lecturers and other staff who seek more intensive collaboration with non-university partners in the context of challenge-based university education, exemplified by Joint Interdisciplinary Projects (JIPs), the City Deal ‘Kennis Maken’ and many other examples. About Reinout Kleinhans Reinout Kleinhans is Associate Professor of Urban Regeneration and Neighbourhood Change at the Faculty of Architecture and the Built Environment, Delft University of Technology. His research and teaching interests and expertise include urban regeneration, citizens’ self-organisation, community entrepreneurship, challenge-based learning and community engagement. Please note We are happy to inform you that this Meet & Eat will be organised in the Teaching Lab. A vegetarian lunch will be provided. Please let us know if you have any dietary wishes. In case you are not able to join the event (last minute), please let us know by sending an email to teachingacademy@tudelft.nl . Click here to sign up

ABP Pension Information Meeting April

ABP Pension Information Meeting April 05 April 2022 10:00 till 14:30 - Location: Online Your ABP Multi optional Pension! Our society is constantly changing and your pension is changing with it. Changes in State pension ages, pension accrual and choices when you retire often make retirement a difficult subject. For many people, retirement seems a long way off, for others it is getting closer and closer. Either way, it is important to delve into your pension. And to get answers to questions like: Can I retire sooner, or later? What is conditional pension, and what should I look out for? How much pension and State pension do I accrue? How much pension can I have paid out if I retire? What happens to my pension if I work less? What is surviving dependents pension and what can I do with it? I want to make calculations myself: how does MIJNABP work? Do you have these or similar questions? Retirement is important As an employer, we think it is important that you know what the possibilities are with your ABP pension. That is why, in cooperation with ABP, we have organized an online presentation. During this meeting you will receive answers to the above questions.You can follow the presentation at home, or in the workplace, through Microsoft Teams. Microsoft Teams also offers the opportunity to ask questions to the ABP pension officer during the presentation, which can be done both verbally and through chat functionality.. However, the presentation is not intended to elaborate on personal case studies. Who? International employees and their partners at TU Delft who are interested in learning more about the Pension System in the Netherlands. When? 5 April 2022 - 10.00 to 11.30 for employees < 55 years. Sign up for this online presentation? CLICK HERE Participants are asked to sign in to Microsoft Teams 10 minutes before the presentation starts so that the presentation can start on time.

Look back DEWIS Virtual Coffee February

Thanks to all the participants of the last DEWIS (online) Coffee Meeting in February! We had a great discussion and reflection about challenges and benefits of remote working during the Pandemic. It was nice to see that in the end, despite being a hard time for everyone we all were able to go through the challenge and grow stronger than before. We are all strong resilient women of science!! During the talk common and similar experiences and stories have been shared by the participants and here below (Figure 01) we captured some of the insights and personal stories shared. Figure 01. Personal Stories & Experiences shared by the participants during the last coffee meeting After that, we discussed and brainstormed together: ‘How can we foster a ‘Culture of Care’ within universities?’ Figure 02. Insights captured during the discussion of the last coffee meeting. In conclusion we all agreed that we need to create a network of support and being supporters for each other , always asking your peers and colleagues how they feel and offer your help. Don’t be afraid of reaching out if you need help yourself or simply need to chat with someone for some company! We are all on the same boat, we all go through difficult moments and we all need human contact to thrive and feel alive. In Figure 2 we captured some of the thoughts of the discussion. Hopefully, this has been the last Online Meeting and from next ones we can meet again in a physical space. Our first upcoming networking event will be our Spring Networking Diner! It was also the last meeting facilitated by Chiara Marradi , who unfortunately moved on in her career (now she lives and works in Belgium). However, she was grateful to be part of this network of inspiring women!

Koen Jurgens joined ImPhys as MSc student

Koen Jurgens is a Molecular and Cellular Life Sciences Msc student from Utrecht University, track Biophysics & Molecular Imaging. He will 3D print phase plates to engineer the point spread function, and consecutively evaluate the performances to optimize the design of these phase plates. His supervisor is Bernd Rieger.

Kornelis Blok in Foodlog over energiecrisis na oorlogssituatie Oekraïne

Door de oorlogssituatie in Oekraïne zijn de energiekosten en brandstofprijzen geexplodeerd. Om het Russisch gas niet meer nodig te hebben komt het Internationaal Energieagentschap (IEA) met een tien-punten-plan.

The Berlage Sessions: On Detail

As part of The Berlage Sessions, Christoph Kumpusch gives the lecture 'On Detail'.

Webinar Remote Teaching | Getting a BOLD Edge: Student Readiness for Learning in a Digital World | 13 April

Webinar Remote Teaching | Getting a BOLD Edge: Student Readiness for Learning in a Digital World | 13 April 13 April 2022 10:00 till 11:00 - Location: Online - By: Teaching Academy This webinar reports why learning how to learn online is now a crucial life skill and cannot be left to chance. It outlines what we know from the research on student readiness for successfully engaging in new forms of blended, on-line and digital (BOLD) learning and shares an innovative effort to help give learners a digital edge for their study. The basic thesis woven throughout the talk is that we can learn a lot on how to design our courses and what it really means to be a BOLD learner by taking more time and creating opportunities to listen to the “voice” of learners. Student Readiness is a focus in the DigitTeL Pro project in collaboration with the 3 courses: ' Synchronous Hybrid ', ' Blended ' and ' Online Distance '. If you are interested in DigiTeL Pro or the courses, the presentation slides of the launch session in November 2021 are available, including the full launch recording : Introduction CPD and DigiTeL Pro by George Ubachs (EADTU – European Association for Distance and Teaching Universities) Student Readiness for Digital Education by Mark Brown (DCU – Dublin City University) Synchronous Hybrid Education by Marieke Pieters (KU Leuven – Katholieke Universiteit Leuven) Blended Education by Naomi Wahls (TU Delft – Delft University of Technology) Online Distance Education by Albert Sangrà (UOC – Universitat Oberta de Catalunya). Future webinars will be announced once the titles and descriptions are finalized. If you have a topic that you would like us to cover, please email Naomi directly: n.l.wahls@tudelft.nl . Join the weekly webinars via MS Teams group

Hans de Bruijn in Trouw over de kracht van toegeven

Hans de Bruijn legt in zijn column uit dat Baudet geen genuanceerd standpunt heeft in zake de oorlog in Oekraine, maar wegkijkt.

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Unconscious Bias session during Summer Introduction Programme (18-22 August 2024)

As part of Summer Introduction Programme , our colleagues Fatima Ait Bari and Stavroula Manolaki of the Diversity & Inclusion (D&I) Office gave an engaging presentation on Unconscious bias. The audience consisted of a group of master’s, exchange and bridging students, many from the international community, arriving at TU Delft this academic year 2024-2025. The session had as a goal to take the students along a “journey” of exploring how unconscious biases are formed, how they influence our interactions, and how we can become more aware of them. Participants were encouraged to reflect on their own biases and consider how they hinder their connection with people with diverse perspectives. Through interactive discussions and scientific insights, the presentation emphasized the importance of focusing on shared similarities to foster inclusive relationships. The D&I colleagues guided the students through a thought-provoking journey, helping them take steps toward greater inclusion and understanding in both academic and social environments. The presentation ended with encouraging the students to “Get together on the basis of our similarities; to grow on the basis of our differences”. We wish all new master, exchange and bridging students a successful and enjoyable academic year at TU Delft!

Fresh from Cafe X, not from the delivery service: food deliveries are not allowed

Geen eten bezorgen bij X
We hebben een nieuwe regel opgenomen in de huisregels van X met betrekking tot het nuttigen van afhaalmaaltijden bij X. Het is niet toegestaan om eten te laten bezorgen door een bezorgdienst en dit op het terrein te nuttigen. Je bent natuurlijk wel van harte welkom in Café X voor een hapje en een drankje.

Equity, Diversity & Inclusion Month 2024

In oktober 2024 viert de TU Delft de EDI-maand met als thema: United for Change, Together We Grow. Gedurende de hele maand biedt het Diversity & Inclusion office in samenwerking met de faculteiten, netwerken en serviceafdelingen workshops, trainingen en andere evenementen georganiseerd door en in de meeste gevallen aangeboden door collega's binnen de TU Delft.

NWO grants funding for innovative research on physical experimental environments

How to move from experiment to mainstream? A consortium led by professor Tamara Metze, has been awarded a prestigious grant from the Netherlands Organisation for Scientific Research (NWO). In search for pathways toward more sustainable futures, Metze and her team will explore how various innovations in field labs such as The Green Village, in urban living labs such as Engy Lab South-East in Amsterdam, and in all sorts of citizens’ initiatives, can be mainstreamed and make more impact on sustainability transitions. Pilot paradox The project ‘From EXperiment to sustainable change: TRAnsformative methodologies for Innovation and learning’ (EXTRA) seeks to overcome a persistent “pilot paradox”. In this paradox, much experimentation takes place but long-term systemic impact remains difficult. Researchers together with all sorts of change makers will synthesise existing knowledge on how to mainstream, upscale, spread, broaden and deepen developed innovations. Tamara Metze: ‘I am excited to unravel what are effective ways of cocreation that lead to mainstreaming the positive changes made in experimental environments. We will figure out how learning and innovation can lead to lasting changes in regulations, policies, and financial systems and the biophysical environment.’ Tamara Metze Read the NWO press release Actionable tools The project is crucial for accelerating sustainability transitions. By refining methodologies for mission-driven experimentation and develop hands on tools for all sorts of change-makers, it will be easier to mainstream the sustainable lessons and innovations. ‘These tools will not only aid grassroots innovators but also influence institutional and organisational structures, ensuring that lessons learned from experiments are better anchored in policies, regulations, and organisations’, explains Metze. The project will employ a transdisciplinary action research approach, bringing together knowledge from various disciplines and policy domains. By co-creating solutions with public and private partners, the research will have an immediate impact. In the long term, the project aims to build a more efficient innovation ecosystem, contributing to more impactful and sustainable outcomes for both society and the environment. Projectpartners TU Delft, VU Amsterdam, Wageningen University & Research, Hogeschool van Amsterdam, Erasmus Universiteit Rotterdam, Hogeschool Rotterdam, The Green Village, AMS Institute; PBL Planbureau voor de Leefomgeving, WoonFriesland, Dijkstra Draisma, Provincie Noord-Holland, Ministerie van Binnenlandse Zaken, PRICE / Almere, BouwLab, Alliantie Samen Nieuw-West, Innovation Quarter.

Interview Eveline Vreede with Digitaal Veilig Den Haag

Eveline Vreede is the Managing Director of our Safety & Security Institute. She is responsible for collaborations, programs and the development of the Safety & Security theme at TU Delft | Campus The Hague. Among other things, she connects the institute with government agencies. Digitaal Veilig Den Haag spoke with her about the institute's activities in the field of digital security.

TU Delft Excellence Fund supports Prof. Stefan de Witte and Dr Anasua Chatterjee

With support from the TU Delft Excellence Fund, two prominent scientists recently started their work at TU Delft. As per September, Prof. Stefan de Witte has been appointed Professor of Optics for Nanoscale Metrology at the department of Imaging Physics.

Researchers Use an EUV Flashlight and Free-Air Diffusion, Plus a Clever Algorithm, to Inspect Chips

Postdoc Yifeng Shao (ImPhys) and his colleagues from Delft and Utrecht University have investigated a new imaging technique using extreme ultraviolet light to study the three-dimensional structures of chips at the nanoscale.

Outstanding Paper Award on Scientific Understanding in RL

M. Suau, M. T. J. Spaan, and F. A. Oliehoek were awarded the Outstanding Paper Award on Scientific Understanding in RL at the first Reinforcement Learning Conference (RLC).

Professor of Urban Design Tess Broekmans: ‘Designers must learn to listen better’

Tess Broekmans, co-owner of Urhahn urban design and strategy, delivered her inaugural address as professor of Urban Design on Friday 6 September. In it, she addressed ‘the complexity of the everyday’. After all, how can designers' visions connect better with people's everyday lives? In doing so, she also sees a new role for area developers.

2 Veni Grants for the ELLIS Unit

In an effort to make new and strengthen existing connections, a delegation of ELLIS Unit Delft visited ELLIS Munich and some of the most renowned AI research institutions in Munich area on the 25th and 26th of January 2024. The delegation consisted of people from TU Delft’s cognitive robotics department, and the sequential decision making group.

Unusual waves grow way beyond known limits

Waves that come from multiple directions are extremer than extreme. These remarkable deep-sea waves can be four times steeper than what was previously imagined, as is shown in research by TU Delft and other universities that was published in Nature today. A long time ago, stories were told of mysterious rogue waves that materialised out of nowhere and could topple even the largest ships. These waves lost their mythical character when the first rogue wave was recorded at the Draupner platform in the North Sea. In 2018, Ton van den Bremer and his colleagues at the Universities of Edinburgh and Oxford managed to recreate the Draupner wave in the lab for the first time ever, and this opportunity to study freak waves closely produced unexpected insights. Multiple waves push up water New research by the research consortium now shows that these remarkable waves do not break when traditional theories hold they should, the secret behind which lies in how they arise. Ton van den Bremer, expert on fluid mechanics at TU Delft and led the study, explains: “When most people think of waves, they think of the rolling waves you’d find on a beach. The type of wave we studied occurs in open water and arises when waves coming from multiple directions come together. When these waves with a high directional spread converge, the water is pushed upwards, forming a partially standing wave. An example of this is known as a crossing wave. How crossing waves arise Under certain conditions at sea, waves from multiple directions occur. This can happen in a place where two seas meet, or where winds suddenly change direction, as in a hurricane. When waves from two directions meet, a cross wave occurs, provided their directions are far enough apart. The study also shows that the further apart the directions are, the higher the resulting cross-wave. Travelling waves break when they reach a certain limit, this is when they reach their maximum steepness. The study shows that waves with a multidirectional spreading can get as much as 80% steeper than this limit before they start breaking, which means they can get almost twice as high as ‘normal waves’ before they start to break. Travelling wave (l) and a wave with high directional spreading (r) Breaking waves that grow Next, the researchers found another highly unusual phenomenon that defies existing theories, a phenomenon that is unprecedented according to Van den Bremer: “Once a conventional wave breaks, it forms a white cap, and there is no way back. But when a wave with a high directional spreading breaks, it can keep growing.” The study shows that these enormous waves can grow to twice their original steepness while breaking, which is already twice bigger than the conventional limit. Together, the waves can grow four times steeper than previously thought possible. Damage to offshore structures The knowledge that multidirectional waves can become as much as four times larger than was deemed possible can help design safer marine structures. "The three-dimensionality of waves is often overlooked in the design of offshore wind turbines and other structures in general; our findings suggest this leads to designs that are less reliable", says Mark McAllister of the University of Oxford, who led the experiments and is now a senior scientist at Wood Thilsted. Innovative vertical sensors made it possible to take accurate 3D measurements of waves. Innovative 3D measurement method A 3D measurement method developed in the FloWave lab paved the way for these new insights. “Conventional 2D wave measurement methods weren’t up to the task”, Van den Bremer explains, which is why the research group designed a new way to create 3D wave measurements. Ross Calvert of the University of Edinburgh: “This is the first time we've been able to measure wave heights at such high spatial resolution over such a big area, giving us a much more detailed understanding of complex wave breaking behaviour." FloWave Ocean Energy Research Facility in Edinburgh. The circular basin has a diameter of 25 metres and can be used to generate waves from multiple directions. Header image by: Fabien Duboc

A strong nose for trouble

Ammonia gas – it is both highly poisonous and corrosive, yet also often used in industry, or present around intensive livestock farming. To better mitigate the risks of ammonia leaks, Paddy French together with Lina Sarro and Sten Vollebregt will make smaller, more robust and eventually more affordable ammonia sensors. The NWO OTP programme has funded their research into a fully-integrated, single-chip sensor that incorporates two porous silicon carbide structures for detecting ammonia and humidity, all in a single layer and one etch step.

Stefan Witte joins Imaging Physics as professor

Delft University of Technology's Executive Board has appointed Stefan Witte as professor of Optics for nanoscale metrology in the Imaging Physics department of the Faculty of Applied Sciences as of September 2024. Thanks to the TU Delft Excellence Fund, Stefan Witte can get off to a flying start with his new research group and expects to obtain the first research results soon.

October 2024: Equity, Diversity & Inclusion Month

Theme: “United for Change, Together we Grow” The EDI Month programme focuses on bringing together people from different backgrounds, perspectives, and opinions to foster an environment where meaningful conversations and innovative ideas can flourish. From interactive workshops on diversity and teamwork to inclusive leadership training, all with an emphasis on “practical learning” and free of charge . Curious about what's on offer? Visit the online calendar for a full overview of the events and sign up.

SPTL contributions at European Transport Conference (ETC) (18-20 September, Antwerp)

The 2024 edition of the European Transport Conference (ETC) will be held from 18-20 September at University of Antwerp, Belgium. The following Smart PT Lab contributions will be presented: Passenger preferences for (emerging) public transport access/egress modes Nejc Gerzinic, Mark van Hagen, Hussein Al Tamimi, Dorine Duives, Niels van Oort [Abstract] - [Slides] An application of Latent Class Analysis to explore the impact of sociodemographics on travel behaviour profiles – the importance of sociodemographics in transport policy Nadine Martje Eichenauer, Niels van Oort, Bert van Wee, Jan Anne Annema [Abstract] - [Slides] Towards a Global Standard for Estimating Life Cycle Greenhouse Gas Emissions from Public Transport Services Marko Kapetanovic, Niels van Oort [Abstract] - [Slides] The full program can be found here: https://aetransport.org/etc/programme

Towards more efficient solar cells, with a lower carbon footprint

The SiLEAN project, funded by the European Union, has officially launched with the goal of setting a new benchmark in solar cell efficiency by over 25.5%, while reducing costs and lowering the carbon footprint by up to 75%.

Ensuring safe and quick food bike-delivery services in cities

Cyclists rushing to deliver food on time to hungry customers is an increasing problem in cities with the growing demand for fast home delivery services. This surge has resulted in more traffic in bike lanes, contributing to accidents and raising concerns about rider safety. In the framework of SINERGI project researchers like Yousef Maknoon are looking into solutions that will help boost logistic operations that are both efficient and safe. ‘Bike delivery services are a great way to transport goods from A to B in a green manner, replacing delivery cars or vans. These micro-delivery systems can really help make city logistics more sustainable,’ says logistics and modelling expert Yousef Maknoon, who is involved in developing real-time decision models for the SINERGI project. Besides looking into sustainability, the project aims to empower delivery providers to offer cost-efficient services, while prioritising the well-being of riders. ‘We want to help bring down the number of accidents,’ stresses Maknoon. Private and public stakeholders have joined to conduct pilot initiatives in the cities of Amsterdam, Shanghai, Singapore and Copenhagen. Yousef Maknoon Safe routing ‘To improve rider safety, the app automatically provides recommended routes when food delivery riders receive their task, helping them avoid dangerous intersections and busy streets. In Amsterdam, the goal is to develop a map that will show the safety of cycling infrastructure. The map is planned to be enriched with real-time information such weather conditions, busy days, and times of the week to not only improve delivery time prediction but also assess route safety in real time,’ explains Maknoon. ‘But everything depends on the cyclist's willingness to take the safer route. When a rider is paid per delivery, they might not be willing to take a longer route. Especially when they know the area well, it can be tempting to take a shorter route that may not always be the safest option.’ A survey held amongst 300 delivery riders found that they can be nudged to follow the recommended routes when they are compensated financially. Profit versus safety Maknoon: ‘What we also found is that paying an hourly fee, instead of paying per on-time delivery, promotes safer riding behaviour, like Just Eat Take​away does in the pilot in Amsterdam. However, other issues arise because riders might not be so motivated to deliver on time. Then you need other incentives to motivate efficiency among riders. Otherwise, customers might switch to other service providers. This puts the business model which is based on hourly payment and prioritize safety, under pressure.’ It seems now that delivery services need to make a trade-off between profit and safety. ‘With the SINERGI project we want to empower delivery providers to offer cost-efficient services while prioritising the well-being of riders.’ Government regulation Public authorities can, for example, improve road safety by enhancing infrastructure, such as building separate bicycle lanes.’ Delivery providers can introduce incentives for riders that compensate the extra time a longer, but safer, route might take. But this puts pressure on profitability and could cause micro-delivery logistics platforms to struggle or even go out of business. It is likely that government regulation will need to play a role in profit-driven societies, as safety risks being overshadowed. Fair delivery system This is also the case for ensuring a fair delivery system where all customers are serviced, whether they live in the busy city centre or the less densely populated countryside. Otherwise, customers who live farther away may not be serviced, as longer cycling times mean less money for riders when they are paid by commission. Riders can simply reject these orders and choose to deliver only to places where they think they can earn more. Human factor In this digitally connected world, we need to consider the human factor in real-time decision-making. The wellbeing of riders, their working conditions, and their quality of life are also important when we talk about making operational decisions. It is interesting to compare the four cities and how they manage the tension between cost-efficiency and safety, and to see what they can learn from each other. About SINERGI SINERGI is a three-year project that runs from 2023 to 2026. It involves thirteen research institutions, governmental authorities, and companies collaborating on a comprehensive framework to improve sustainable city logistics. The project aims to enable real-time management and strategic planning of efficient, safe and user-friendly delivery services. Besides Yousef Maknoon other researchers from TU-Delft involved are: Shadi Sharif Azadeh (project leader), Gonçalo Correia, Kuldeep Kavta and Dongyang Xia. Read more about the SINERGI project.

Causing near collisions with cyclists to improve traffic models

It’s surprising, but in the Netherlands – a nation of cyclists – there’s very little data on how cyclists respond to each other in traffic. Yet this data is essential for creating more realistic traffic models, which in turn are key to designing better cycling infrastructure across the Netherlands. Anna Marbus, a master’s student in robotics, wants to change that by causing near collisions with cyclists.

Contributions of Smart PT Lab at ODS2024 (September 8-12, Badesi, Italy)

From September 8-12, the 2024 edition of the International Conference on Optimization and Decision Science (ODS) was held in Badesi on Sardinia (Italy). The Smart Public Transport Lab contributed to this event with presentations by Rina (Jingyi) Cheng and Renate van der Knaap. Short-term Bike-sharing Demand Forecasting under Multiple Sources of Uncertainties: A Sequential Framework with Multivariate Inputs Jingyi Cheng, Gonçalo Correia, Oded Cats, and Shadi Sharif Azadeh Abstract: A sequential framework is proposed for short-term probabilistic demand forecasting of bike-sharing services, considering uncertainties from public transit systems. Leveraging the transformer-based structure, the proposed solution is generalizable, scalable, and adaptive to new data. Through a case study with Washington data, our preliminary results suggest that the proposed approach enhances forecasting. This work is part of the Horizon-EU SUM project. Multi-period Railway Timetabling to Match Time-dependent Demand Renate van der Knaap, Niels van Oort and Rob M.P. Goverde [Abstract] The full program can be found here: https://www.airoconference.it/ods2024/schedule

Unravelling how DNA is looped with DelftBlue and experiments

Roman Barth Proteins are the molecules that carry out essential functions in our cells, such as compacting long strands of DNA into a tiny structure in the cell nucleus. Experimental biophysicist Roman Barth wanted to understand this process down to the molecular level. Thanks to the DelftBlue supercomputer, he was able to compress several years of experiments into a single year. Knowing the sequence of amino acids that a protein is made of doesn’t tell you its three-dimensional shape. And knowing its shape doesn’t tell you its function and how it interacts with other molecules when performing that function.This is the challenge Roman Barth faced during his PhD at the Cees Dekker Lab in the Bionanoscience Department. “My goal was to unravel the interaction between two proteins known to be involved in the compaction of DNA via a process called DNA loop extrusion,” he says (see video ). “The first protein, cohesin, will loop DNA continuously if unstopped. The second protein, CTCF, acts as a stop sign to cohesin. That is very important for the cell as DNA, for example, needs to be accessible when read, expressed or maintained.” This is how scientists think cohesin loops DNA The interactions between proteins can’t be calculated from their amino acid sequences using first principles. AlphaFold The interaction between the two proteins depends on their shape, the parts that are in close proximity, and the forces that then occur between groups of atoms. “These can’t yet be calculated from their amino acid sequences using first principles,” Roman says. “And while CTCF is a relatively short protein, cohesin is a complex of five subunits which it can exchange – allowing for many configurations and many more interactions.” At the start of the project in 2023, it looked like a brute-force experimental approach was the only way to go. But then AlphaFold came along. “AlphaFold is an algorithm, based on artificial intelligence, that can predict the structure of proteins from their sequence,” Roman says. “It completely changed our approach. We could now make predictions about what our proteins would look like, and what may happen to them when they meet. Instead of experimentally testing all possible configurations of CTCF and cohesin, we could ask the computer to predict likely interactions and test only those.” Project storage allows multiple users from various departments to share resource-intensive installations on DelftBlue. Powerful computer AlphaFold did come with the new challenge of requiring a powerful computer to run on – a lot of disk space to store the 5 Tb database it browses and a lot of computing power to run the algorithm. “It is almost impossible to run AlphaFold on a laptop or desktop and we lacked the expertise to build our own cluster. So, our second lucky break was that DelftBlue came online.” It also turned out that another researcher, Marcel van der Broek from Biotechnology, had already installed AlphaFold on DelftBlue. Rather than having every user install their own version, the DelftBlue administrative team setup what is now called project storage. “It allows multiple users, from various departments, to share such resource-intensive installations. Marcel and I were the first to make use of this feature for AlphaFold.” Cluster newbie Roman was still pretty much new to using a computational cluster when he started with DelftBlue, but he quickly found his way. “DelftBlue has an intuitive interface, great documentation, and a very knowledgeable and helpful support team,” he says. “You can basically figure it out from there.” He avoided running into the 5-day runtime limit for jobs submitted by breaking up the CTCF protein into smaller fragments. “Still, it would be nice for DelftBlue to have even bigger GPUs or to be able to use multiple GPUs at the same time, especially for tasks involving artificial intelligence.” One thing he really appreciated was that the DelftBlue administrators were very open to users trying out new things. “Their attitude of ‘seems to be useful, we’ll give you the resources you need’ has been very helpful,” Roman says. And when he ventured into new DelftBlue territory, such as when he submitted hundreds of jobs at once, the administrators were just as curious about how the cluster’s performance. “Turns out the job allocation scheduler handled it well.” Testing everything purely experimentally would have taken us at least three times as long. Two likely interactions Using AlphaFold and DelftBlue, Roman was able to pre-screen hundreds of different combinations. In this way, two likely interactions were identified. These were validated in laboratory experiments in which he looked for how these two fragments of the CTCF protein affected the DNA looping process. “Even though any such fragment can nowadays be quite easily purified from cells, performing the necessary experiments still took about 6 months. All in all, this project took us a year from start to finish, whereas testing everything purely experimentally would have taken us at least three times as long.” Having obtained a Schmidt Science Fellowship, Roman will next undertake a postdoc in at the University of Washington in Seattle, delving much further into AlphaFold and protein structure prediction. “My time at TU Delft and with DelftBlue has been a fantastic preparation for this next step in my career. And I hope the administrators of the supercomputer over there will be just as open-minded and helpful.” Rendering of a CTCF fragment bound to a cohesin-subunit.