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

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).

News

25 November 2021

BEI Best MSc Graduate 2021: Alicia Rodríguez Molina!

BEI Best MSc Graduate Awards 2021 Since 2020, Delft Bioengineering Institute (BEI) organizes a cross-campus competition for MSc students who performed remarkably well at their graduation projects in bioengineering. This year, sixteen very impressive theses were submitted. After a strenuous review and discussion, the jury finally agreed that Alicia Rodríguez Molina (MSc Life Science & Technology), Akash Singh (MSc Computer Science) and Jette Bloemberg (MSc Mechanical Engineering) have delivered the most innovative, interdisciplinary bioengineering projects of 2021. On top of eternal fame, they will receive personal cash prizes of €1000, €500 and €250. 1. Alicia Rodríguez Molina (MSc Life Science & Technology) Thesis: "TPR-CHAT is a caspase-like protease that forms a complex with the CRISPR-Cas type III-E endoribonuclease effector gRAMP” Daily supervisor: Sam van Beljouw (Applied Sciences, Bionanoscience) Thesis Committee: Stan Brouns (AS/BN), Peter-Leon Hagedoorn (AS/Biotechnology), Chirlmin Joo (AS/BN) “Alicia has made large contributions to our research discovering a new CRISPR-Cas system with potentially profound implications and new applications. She has been responsible for the major discovery that links a protease (protein cleaving enzyme) to CRISPR-Cas for the first time. The protein complex she identified was named Craspase and can likely trigger cell suicide in bacteria to protect bacteria from virus infection. We anticipate that Craspase can be converted to a tool for applications in molecular diagnostics, targeted knockdown of gene expression and biomolecule activation or deactivation in cells. A patent was also filled to protect some of these ideas. Importantly, her findings were included in a paper published in Science August 26 (attached) on which she was third author.” 2. Akash Singh (MSc Computer Science) Thesis: “Unsupervised Manifold Alignment with TopoGAN” Thesis Committee: Marcel Reinders (EWI/Pattern Recognition and Bioinformatics), Christoph Lofi (EWI/Web Information Systems), Ahmed Mahfouz (EWI/PRB and LUMC/Radiology), Tamim Abdelaal (LUMC/Radiology) “In his thesis, Akash developed TopoGAN, a deep learning method to solve the challenging task of integrating single cell datasets with no matching samples (i.e. cells) or features. Akash’s thesis proposes multiple innovative ideas to address this challenge. First, Akash showed that Topological Autoencoders can capture the heterogeneity of single cell data better than current approaches such as (variational autoencoders, tSNE and UMAP). This on its own is a significant contribution to the field. Second, Akash proposed an approach to tackle the instability of GAN methods in the task of manifold alignment, which can be generally applied in other fields of machine learning. Third, in evaluating the performance of his method, Akash showed that current strategies have severe shortcomings and should as such be revised to faithfully reflect the performance of different methods.” 3. Jette Bloemberg (MSc Mechanical Engineering) Thesis: “MRI-Ready Actuation System for a Self-Propelling Needle” Supervisors: Fabian Trauzettel (3mE/Biomechanical Engineering), Dimitra Dodou (3mE/BmechE), Paul Breedveld (3mE/BmechE) Thesis Committee: Paul Breedveld (3mE/BmechE), Fabian Trauzettel (3mE/BmechE), Dimitra Dodou (3mE/BmechE), Matthijs Langelaar (3mE/Precision and Microsystems Engineering), Jovana Jovanova (3mE/MTT) “Jette did a very interesting research into a new kind of self-propelled steerable needle for prostate interventions under MRI. She developed a perfectly working prototype, bio-inspired on the anatomy of parasitic wasps. (…) Based on a past PhD project in which we developed novel, self-propelling needles based on the ovipositor-anatomy of parasitic wasps, Jette brought this research to an entirely new level. In her project we wanted to evaluate ovipositor-inspired needles on human prostate tissue under MRI. This means that the design should not contain any metallic parts that react on the powerful magnetic MRI-field. To solve this issue, Jette designed an entirely novel manually-driven propulsion mechanism that she printed from plastic on Formlabs and Ulitimaker 3D-printers, thereby gaining a lot of know-how on how to design complex mechanisms with tight tolerances using 3D printers. Driven by her novel propulsion mechanism, Jette designed a very thin (Ø0,81mm) ovipositor needle composed out of six individually moveable NiTi rods. For the experiments in human prostate tissue, Jette set up a very close collaboration with a well-known urology group at the Amsterdam University Medical Center (AUMC), headed by Dr. Daniel Martijn de Bruin. Jette organised many meetings with this group, arranging human prostate tissue, and using an MRI-laboratory scanner at the AUMC for her experiments. As the space within this MRI-scanner was limited, she also developed a special experimental facility in which the tissue could be stored and moved with near zero friction.”