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

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

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.

15 January 2016

Algae prove promising candidates for biodiesel production via 'survival of the fattest'

Smart methods for cultivating algae bring the efficient production of biodiesel using algae in sight. On Tuesday 19 January, Peter Mooij will obtain his doctorate at TU Delft for his work on this subject. CO 2 neutral There is huge scientific interest in the use of microalgae to produce carbohydrates and in particular lipids (fats), as lipids from microalgae can be converted into biodiesel. The amount of CO 2 released by the combustion of this biodiesel is equal to the amount of CO 2 that was previously extracted from the atmosphere by the microalgae. Thus the use of biodiesel does not lead to an increase in CO 2 in the atmosphere. 'Microalgae offer two huge advantages over other biological oil production platforms', says doctoral candidate Peter Mooij from TU Delft. 'Firstly, after cultivation, microalgae can be made up relatively largely of lipids. And secondly, relatively little fresh water and agricultural land is required to cultivate microalgae.' Survival of the fattest Mooij uses a smart method to cultivate suitable algae that is economically viable for large-scale algae production: survival of the fattest. The fattest algae survive. 'In the reactor we give a competitive advantage to the algae with the required characteristics, in this case the production of carbohydrates and fats. We start with a collection of 'ordinary' algae. During the day we provide them with light and CO 2 . This is enough for them to produce oil, however they are unable to divide. They need nutrients for cell division and they are only given these in the dark. To absorb these nutrients, the algae need energy and carbon. This means that only the fattest algae can divide, as they have stored these during the day. By removing some of the algae every day, the culture will eventually exist of only the fattest algae.' Starch 'All of our experiments led to systems in which carbohydrates (starch) formed the primary energy storage compounds', continues Mooij. 'So we have found a suitable environment in which carbohydrate production by algae is rewarded.' Unfortunately this environment is not yet selective for the storage of fats. The culture environment needs to be made even more specific to achieve this. 'But a greater understanding of the ecological role of lipids and carbohydrates in microalgae clears the way for the creation of lipid-specific selective environments. Rewarding a microalga for showing the desired behaviour by using a selective environment, one of the central concepts in my research, will be shown to be a valuable approach once there is a better understanding of the ecological role of lipids.' More information For further information please contact Peter Mooij tel. +31 6 - 483 826 35 or p.r.mooij@tudelft.nl or Wendy Batist, press officer TU Delft via tel. +31 - 15 - 27 884 99 or g.m.batist@tudelft.nl . Please read Peter Mooij's blogs on Faces of Science (only in Dutch).