Biotechnology

Innovation is crucial to fulfil the potential of industrial biotechnology for sustainable production of fuels, chemicals, materials, food and feed. Similarly, scientific and technological advances in environmental biotechnology are needed to enable novel approaches to water purification, and ‘waste-to-product’ processes thus contributing to a circular economy. Increased fundamental knowledge encompassing enzymes, microorganisms and processes are essential for progress in this field. The Department of Biotechnology covers this research area and, based on new insights, selects, designs and tests new biobased catalysts, micro-organisms, and processes.

The department encompasses five research sections:

News

15 December 2020

Five 20k grants for cross-campus bioengineering research projects

In response to the first call for bioengineering research proposals, Delft Bioengineering Institute received a stunning amount of thirteen interfacultary proposals. After a thorough peer review process, eight very good to excellent proposals surfaced. From these, MT BEI has selected the five winning projects listed below. We want to thank all BEI PIs for submitting proposals and all reviewers for their efforts, knowing they were all quite busy already. We hope that 2021 will see the start of a second five-year term for the institute, so we can continue to support these promising cross-campus collaborations! >> Biochars for reducing methane emissions Methane has a high global warming potential, and landfill is one of the largest contributors of global human-caused methane emissions. Methane treatment using engineered microbial oxidation systems is one of the ways to reduce these emissions. Biochars, carbon-rich materials produced from sources such as municipal solid wastes, wastewater sludge and wood, have gained interest in the waste management industry as media to enhance control of landfill gas emissions. In this project, led by Julia Gebert of Geoscience & Engineering (CiTG), BEI PIs of four TU Delft faculties team up to investigate the potential of biochars for enhancing microbial methane oxidation in biofilters. Project title: Effects of biochar on the performance of microbial CH4 oxidation in biofilters to reduce landfill gas emissions. BEI PIs: Julia Gebert (CiTG/GSE), Wiebren de Jong (3mE/P&E), Aljoscha Wahl (TNW/BT), Martin Pabst (TNW/BT), Thomas Abeel (EWI/Bioinformatics) >> Regenerating neuronal circuits using ultrasound People suffering from neurodegenerative disorders such as Alzheimer’s, Parkinson’s Disease and Multiple Sclerosis, have impaired neuronal circuits. Generation of new neuronal circuits by using a patient’s own stem cells may prove helpful in treating the disease. One of the difficulties in inducing neurons from stem cells, is the low efficiency rate we are able to achieve so far. In this project, BEI PIs Tiago Costa of Microelectronics (EWI) and Dimphna Meijer of Bionanoscience (TNW) join forces to explore the use of ultrasound for effectively building active neuronal networks from stem cells. Project title: SoundCircuit: Regeneration of neuronal circuits using ultrasound BEI PIs: Tiago Costa (EWI/ME), Dimphna Meijer (TNW/BN) >> Medical implants to investigate cell mechanobiology In order to study the cell’s behaviour and differentiation, we need to be able to measure the mechanical, electrical and biochemical signals that are dynamically transmitted throughout the cells. This requires the creation of biomaterial models equipped with different sensor types. In this project, BEI PIs Mohammad J. Mirzaali of Biomechanical Engineering (3mE) and Massimo Mastrangeli of Microelectronics (EWI) will team up to design, fabricate and test the proof-of-concept for medical implants equipped with force sensors that can reach a sensitivity level of one micronewton, so the mechanobiology of cells can be effectively investigated. Project title: Sixth Sense Biomaterials BEI PIs: Mohammad J. Mirzaali (3mE/BM), Massimo Mastrangeli (EWI/ME) >> Advanced cellular nanoimaging Structural biology has been essential in understanding the cell. Studying the dynamics of biological systems requires advanced imaging tools, particularly those that can bring both high spatial and temporal resolutions. In this project, BEI PIs Chirlmin Joo of Bionanoscience (TNW) and Carlas Smith of Delft Centre for Systems and Control (3mE) will join forces to develop a novel methodology for fast absolute FRET distance measurement, taking advantage of smFRET (fast but biased molecular dynamics) and localization microscopy (unbiased but static localization). Project title: New structural biology by integrating nanoscopy and single-molecule Forster resonance energy transfer BEI PIs: Chirlmin Joo (TNW/BN), Carlas Smith (3mE/DCSC) >> 3D-printing bacterial electrodes for CO2 conversion In order to achieve a sustainable future, we need to use abundant molecules such as CO2, water and renewable electricity to create our organic chemicals and fuels. Microorganisms have the ability to enable upgrading of CO2 by microbial electrosynthesis. In this project, Ludovic Jourdin of Biotechnology (TNW) and Kunal Masania of the Shaping Matter Lab (LR) will team up to explore strategies to shape carbon electrodes into hierarchical porous electrodes for microbial electrosynthesis and study the role of hierarchical porosity on microbial and electrochemical activity. Project title: BACTRODE: Hierarchical 3D-printing of bacterial electrodes for breakthrough in CO2 conversion BEI PIs: Ludovic Jourdin (TNW/BT), Kunal Masania (LR/SML)

04 December 2020

In Memoriam: Prof.dr.ir. Herman van Bekkum (1932 – 2020)

It is with great sadness that I inform you of the passing away of our esteemed professor emeritus Herman van Bekkum on 30 November 2020. Herman van Bekkum was Rector Magnificus of Delft University of technology from 1975 to 1976 and worked at TU Delft from 1955 to 1998. During this time, he worked for Shell for a brief period between 1959 and 1961, but he ultimately chose to make TU Delft his home, and a very successful choice that was. After his retirement in 1998 he remained active in our faculty for many years, both within Chemical Engineering and the catalysis community. He meant a lot to the university, especially to the Faculty of Applied Sciences. Herman van Bekkum was a versatile chemist with a near limitless zest for work. He made major contributions to science, especially in the field of catalytic applications of zeolites and ordered mesoporous materials and non-food applications of sugars. More importantly, his infectious enthusiasm conveyed his love of organic chemistry to colleagues and students alike, and enabled him to inspire great achievements in them. This quality was rewarded in 1996 when TU Delft named him a Professor of Excellence. Herman van Bekkum always sought co-operation with industry, and managed to secure extensive funding that he could put towards satisfying his enormous creativity and curiosity. He performed various managerial positions within and beyond TU Delft. Within TU Delft he served as Rector Magnificus in the 1975-1976 academic year, and beyond the confines of the university his positions included that of president of the Royal Netherlands Chemical Society (KNCV). From 1995, he was a member of the Royal Netherlands Academy of Arts and Sciences (KNAW), an important academic distinction. In 1980, he was appointed an honorary member of the Technologisch Gezelschap (TG) study association. Enthusiasm, enormous commitment, efficiency in an environment that sometimes verged on the chaotic, and great mental speed and agility characterised his unique personality. Staff members at the faculty of Applied Sciences often had their work cut out keeping up with him in the corridors. And he never failed to track down the exact documents he needed in his crammed study. Herman van Bekkum will be in our memory always, a memory that will be cherished by all at the faculty who had the pleasure of meeting him or working with him. Our sincerest condolences go out to his family. Paulien Herder, ChemE Departmental Director

01 December 2020

Best Bioengineering MSc Graduate 2020: Nemo Andrea!

“An outstandingly talented biophysicist who seamlessly combines deep biological knowledge with a strong ability for physical abstraction and numerical analysis.” This is how supervisors Marileen Dogterom and Arjen Jakobi (Applied Sciences, Bionanoscience) describe MSc Applied Physics graduate Nemo Andrea. With his thesis “Actin-Microtubule crosstalk studied by cryo electron microscopy” (graded 9.5), Nemo has won Delft Bioengineering Institute’s BEI MSc Graduate Award 2020, comprising of a €1000 personal cash prize. Runners up are MSc Nanobiology graduate Christos Gogou (second prize, €500) and MSc Life Science and Technology graduate Allison Wolder (third prize, €250). Cytoskeleton ‘Actin-microtubule crosstalk’ refers to the functional interactions that exist between these two cytoskeletal systems in living cells. An increasing number of molecular crosslinkers responsible for these interactions are being identified, but detailed mechanistic knowledge on how they connect cytoskeletal filaments is missing. Such knowledge is of great importance for efforts that aim to engineer artificial cells with active cytoskeletal networks from the bottom up. Cryo-EM Taking advantage of recent advances in cryo-electron microscopy, Nemo set out to visualize the architecture of microtubule-actin filament interactions in the presence of an engineered crosslinker. These high-resolution images give valuable insight into how these two filaments affect each other’s dynamic properties, something that was phenotypically observed before with fluorescence microscopy, but not understood at the structural level. In addition, Nemo explored new artificial intelligence methods to reduce the noise level of his cryo-EM images, and independently adapted the algorithm to improve its performance. While the data are too preliminary in terms of statistics to be immediately publishable, the results obtained are completely novel and important for future research in this field. Runners-up Excellent Master thesis work was done as well by runners-up Christos Gogou and Allison Wolder. A short description of their research can be found below. Overall, Delft Bioengineering Institute was impressed by the quality of the ten reports that were submitted, and had a very hard time making a selection. We want to thank all students for their outstanding efforts, and their supervisors for composing their nominations. We hope 2021 will see the start of a second five-year term for the institute, so we can continue to stimulate promising research in the field of bioengineering. BEI Best MSc Graduate Awards 2020 Nemo Andrea – “Actin-Microtubule crosstalk studied by cryo electron microscopy” Supervisors: Marileen Dogterom and Arjen Jakobi (Applied Sciences, Bionanoscience) Taking advantage of recent advances in cryo-electron microscopy, Nemo set out to visualize the architecture of microtubule-actin filament interactions in the presence of an engineered crosslinker. In addition, Nemo explored new artificial intelligence methods to reduce the noise level of his cryo-EM images, and independently adapted the algorithm to improve its performance. Christos Gogou – “Constructing a cryo-EM assay for molecular voltage-sensitivity of liposome-reconstituted membrane proteins” Supervisor: Dimphna Meijer (Applied Sciences, Bionanoscience) Christos bioengineered a novel assay to test if neuronal proteins are sensitive to voltage fluctuations. More specifically, he designed lipid-based vesicles that can be tuned to any membrane potential of choice. Neuronal membrane proteins can then be inserted in these vesicles and visualized at high resolution by cryo-electron microscopy. This assay mimics the action potential of neurons in vitro. Allison Wolder – “Scaling up ene reductase-catalysed selective asymmetric hydrogenation” Supervisor: Caroline Paul (Applied Sciences, Biotechnology) Allison worked on scaling up an incredible enzymatic reaction: hydrogenation. This is notoriously difficult to do, and it requires exploration of the mechanism of the enzyme and its stability. She carried out her thesis in the front seat, thinking outside of the box, suggesting new approaches, making new connections with external companies. The presentation and report were of excellent quality. If you would like to read a thesis, please send a message to N.vanBemmel@tudelft.nl and you will receive a copy.

News

07 April 2016

Two ERC Advanced Grants for TU Delft researchers

Two TU Delft researchers have been awarded an ERC Advanced Grant. Yuli Nazarov and Jack Pronk will both receive this European grant, which is only awarded to five-year projects conducted by internationally established research leaders. Higher-dimensional topological solids realized with multi-terminal superconducting junctions Prof. Yuli Nazarov of the Kavli Institute of Nanoscience (Applied Sciences) will receive an ERC Advanced Grant of €1.5 million for his research proposal on HITSUPERJU (Higher-dimensional topological solids realized with multi-terminal superconducting junctions). His project focuses on topological materials: materials that exhibit the properties of conductors and insulators simultaneously in certain states. Topological materials were only discovered relatively recently, and they have since become a hot topic in the world of solid-state physics. These exotic materials are fundamentally interesting and also hold promise for concrete applications (such as a quantum computer based on Majorana fermions). However, they are very difficult to prepare and control. Yet some properties of topological materials can be closely simulated using a multi-terminal superconducting junction. Nazarov will put together a team of theorists to investigate this and formulate concrete suggestions for experiments and applications. Eliminating Oxygen Requirements in Yeasts Prof. Jack Pronk of the Department of Biotechnology (Applied Sciences) will receive an ERC Advanced Grant of €2.5 million to conduct research on the oxygen requirements of yeasts and fungi. The project, entitled ELOXY (Eliminating Oxygen Requirements in Yeasts), aims to shed light on the as yet unanswered question of why many yeasts and fungi need molecular oxygen. Even when these micro- organisms can obtain plenty of energy from anaerobic fermentation processes, they still need small amounts of oxygen - and nobody knows why. This conundrum is not only of scientific interest, but is also relevant for large-scale application of yeasts and fungi in anaerobic industrial processes.

03 March 2016

A sustainable, good, affordable Hib vaccine for every child

With her doctoral research, TU Delft doctoral candidate Ahd Hamidi has made a major contribution to developing an innovative, scalable, affordable version of the Haemophilus influenzae (Hib) vaccine developed by Intravacc. This low-cost vaccine has now been used to protect 200 million children worldwide against Hib diseases such as meningitis, pneumonia, sepsis and otitis media. Hamidi has defended her dissertation at TU Delft on Thursday 3 March. Gram stain of Haemophilus influenzae type b bacterium Since the 1990s, children in high-income countries have been vaccinated on a large scale with Hib vaccine, which protects against Hib diseases such as meningitis. Since 1993, the Hib vaccine has also been included in the Dutch National Vaccination Programme. ‘The introduction of Hib-vaccine in developing countries was slow, mainly because of its relatively high price. Further, the local vaccine manufacturers didn’t had access to the technology needed for the production of the vaccine’, says Hamidi. In Intravacc’s Hib project she worked on process development, making a major scientific and social contribution to the availability of approved registered low-cost Hib vaccine. Her dissertation also discusses ways of optimising the process and thus reducing the cost price still further, an attractive option for both current or future partners want. Technology transfer and price reduction Hamidi’s research focused on process development and technology transfer to vaccine manufacturers in developing countries, and using mathematical models to improve process knowledge and investigate whether further process optimisation (cost reduction) is possible. In 2013, one of Intravacc’s partners marketed the Hib vaccine, as part of a combined vaccine including four others, through UNICEF at a price that was three times lower than that of existing Hib vaccines, thus bringing it within reach of large numbers of children. If a further price reduction can be achieved, the countries concerned would be able to bear the cost of the vaccine themselves in future. The knowledge gained in the Hib project has meanwhile been transferred successfully to local manufacturers in Indonesia, China (via Korea) and India. UNICEF and GAVI (the Global Alliance for Vaccines and Immunisation) are both involved in distributing the vaccine. Mathematical models Hamidi collaborated closely with experienced process designers and vaccine experts at such institutions as Intravacc (formerly the Netherlands Vaccine Institute (NVI) and the National Institute for Public Health and the Environment (RIVM)) and with various vaccine manufacturers in Indonesia, China, Korea and India. She used the Delft process design method and the knowledge of experts at TU Delft to develop the mathematical models. This enabled predictable models of the Hib process developed and performing sensitivity analyses on the Hib process, thus showing the impact of particular choices on cost. ‘This approach can help both current and future Hib partners to make choices, for example between the use of existing production facilities and building new ones, or the optimum scale of production,’ explains Hamidi. Other vaccines This rational Delft method of process design, says Hamidi, can also be used very efficiently to develop other vaccines. While the process was being developed it was decided to protect it with a patent: partners have a license and their production method protected. More information After graduating in Chemical Engineering (MSc) and Bioprocess Design (PDEng) at TU Delft, Hamidi started working for the forerunners of Intravacc as a process technologist and subsequently project manager and technology transfer expert. In her dissertation she shares the lessons learned from the Hib project so that similar technology transfer projects can benefit from the experience. The project will help to reduce child mortality, one of the UN Millennium Development Goals. Hamidi published in the renowned journal Biotechnology Process in January 2016: ‘ Process development of a new Haemophilus influenzae type b conjugate vaccine and the use of mathematical modeling to identify process optimization possibilities ’ Contact For more information about the dissertation 'Towards a sustainable, quality and affordable Haemophilus influenzae type b vaccine for every child in the world' , please contact A. Hamidi MSc, A.Hamidi@tudelft.nl / Ahd.Hamidi@intravacc.nl tel. +31 30 2742066 or Claire Hallewas (TU Delft Press Officer), c.r.hallewas@tudelft.nl , +31 6 4095 3085.
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