Author Archives: Jen Vanderhoven

£25,000 Proof-of-Concept Available

£25,000 Proof-of-Concept Available

As a result of our last Proof-of-Concept call, and some under-spend, we have £25,000 of PoC funding remaining (@80%fEC). Therefore, we are inviting applications from our members for a final PoC project.

Details: To allow consortia to generate the preliminary information required to establish the feasibility of their proposed approaches, with the target of generating competitive bids to other relevant funding calls.
Important dates: CALL OPEN UNTIL 12 NOON MAY 31st 2017
Amount available: £25,000 (@80% fEC) to fund ONE project.
Further information

CBMNet goes International

We are pleased to announce that we have successfully been awarded funding from the BBSRC to expand CBMNet activities across the globe!


We are headed to New Zealand for a workshop aimed at ‘Exploiting Algae and marine biomass for Industrial Biotechnology and Bioenergy’

In August 2017, CBMNet and PHYCONET members are heading to the Cawthron Institute, Nelson, New Zealand. The workshop focuses on a deeper understanding of the bottlenecks in producing polysaccharides, other bioactives and functional food ingredients from marine biomass. We will identify the challenges in characterisation, production and commercialisation, with the aim of generating project ideas to overcome yield-restricting bottlenecks in this process. The workshop will provide a forum for leading academic and industrial practitioners to establish a strong evidence-based assessment of our current understanding of the challenges and these will be carried forward by establishing new partnerships and collaborations.


CBMNet Co-Director, Dr Gavin Thomas, is planning a UK-Taiwan exchange to understand the structure & function of bacterial transporters for Industrial Biotechnology & Bioenergy.

The transport of small molecules across bacterial membranes via active transport is an underexploited component of metabolic engineering and has great potential in improving processes in industrial biotechnology and bioenergy (IBBE). To be able to rationally improve transporter function, knowledge of the structure/function relationships within these proteins is crucial. In this network we seek support to build a UK-Taiwan network of researchers sharing expertise in the study of transporters relevant for IBBE. The main component of the collaboration is the exchange of knowledge, in terms of understanding the function and structure of membrane transport proteins, in particular in scoping new research into IBBE-relevant targets and developing new techniques and expertise using TRAP transporters. This will be supported through three main activities; A Kick-off meeting July in York, several research exchanges and a grant writing and future perspectives meeting.


We’re welcoming Canadian and European Colleagues to Establish International Partnerships in Industrial Biotechnology and Bioenergy in improved glycoform-based biopharmaceutical production in plants.

This September we are hosting a 3 day workshop which will provide a forum to facilitate collaboration between international partners in developing ‘non-traditional’ expression systems, focusing on plant and yeast cell factories, developing capabilities that can translate to existing and future platform technologies for production of biopharmaceuticals. A key goal of this meeting is to explore opportunities for collaboration and funding within the BBSRC priority funding area ‘New approaches to industrial biotechnology’. Specifically, this workshop will focus on a deeper understanding of the native glycosylation machinery and the manipulation thereof for the production of biopharmaceutical products with enhanced or even novel functions.  The programme will draw on the extensive experience in plant and yeast-based systems and approaches developed to achieve predictive modification of glycoform. Invited speakers have been chosen based on their expertise in different areas of plant and yeast biology, glycosylation, protein biochemistry and cell trafficking.  A key aim of the workshop is to develop a new network of research groups interested in industrial biotechnology and identify common research goals for responsive mode funding opportunities.


 

Microbial response to environmental stresses: from fundamental mechanisms to practical applications

Microbial response to environmental stresses: from fundamental mechanisms to practical applications

Environmental stresses are usually active during the process of microbial fermentation and have significant influence on microbial physiology. Microorganisms have developed a series of strategies to resist environmental stresses. For instance, they maintain the integrity and fluidity of cell membranes by modulating their structure and composition, and the permeability and activities of transporters are adjusted to control nutrient transport and ion exchange. Certain transcription factors are activated to enhance gene expression, and specific signal transduction pathways are induced to adapt to environmental changes. Besides, microbial cells also have well-established repair mechanisms that protect their macromolecules against damages inflicted by environmental stresses. Oxidative, hyperosmotic, thermal, acid, and organic solvent stresses are significant in microbial fermentation. In this review, we summarize the modus operandi by which these stresses act on cellular components, as well as the corresponding resistance mechanisms developed by microorganisms. Then, we discuss the applications of these stress resistance mechanisms on the production of industrially important chemicals. Finally, we prospect the application of systems biology and synthetic biology in the identification of resistant mechanisms and improvement of metabolic robustness of microorganisms in environmental stresses.

Read the full article here.

Improved n-butanol production via co-expression of membrane-targeted tilapia metallothionein and the clostridial metabolic pathway in Escherichia coli

Improved n-butanol production via co-expression of membrane-targeted tilapia metallothionein and the clostridial metabolic pathway in Escherichia coli

Background

N-Butanol has favorable characteristics for use as either an alternative fuel or platform chemical. Bio-based n-butanol production using microbes is an emerging technology that requires further development. Although bio-industrial microbes such as Escherichia coli have been engineered to produce n-butanol, reactive oxygen species (ROS)-mediated toxicity may limit productivity. Previously, we show that outer-membrane-targeted tilapia metallothionein (OmpC-TMT) is more effective as an ROS scavenger than human and mouse metallothioneins to reduce oxidative stress in the host cell.

Results

The host strain (BUT1-DE) containing the clostridial n-butanol pathway displayed a decreased growth rate and limited n-butanol productivity, likely due to ROS accumulation. The clostridial n-butanol pathway was co-engineered with inducible OmpC-TMT in E. coli (BUT3-DE) for simultaneous ROS removal, and its effect on n-butanol productivity was examined. The ROS scavenging ability of cells overexpressing OmpC-TMT was examined and showed an approximately twofold increase in capacity. The modified strain improved n-butanol productivity to 320 mg/L, whereas the control strain produced only 95.1 mg/L. Transcriptomic analysis revealed three major KEGG pathways that were significantly differentially expressed in the BUT3-DE strain compared with their expression in the BUT1-DE strain, including genes involved in oxidative phosphorylation, fructose and mannose metabolism and glycolysis/gluconeogenesis.

Conclusions

These results indicate that OmpC-TMT can increase n-butanol production by scavenging ROS. The transcriptomic analysis suggested that n-butanol causes quinone malfunction, resulting in oxidative-phosphorylation-related nuo operon downregulation, which would diminish the ability to convert NADH to NAD+ and generate proton motive force. However, fructose and mannose metabolism-related genes (fucA, srlE and srlA) were upregulated, and glycolysis/gluconeogenesis-related genes (pfkB, pgm) were downregulated, which further assisted in regulating NADH/NAD+ redox and preventing additional ATP depletion. These results indicated that more NADH and ATP were required in the n-butanol synthetic pathway. Our study demonstrates a potential approach to increase the robustness of microorganisms and the production of toxic chemicals through the ability to reduce oxidative stress.

Read the full article here.

Systems-level understanding of ethanol-induced stresses and adaptation in E. coli

Systems-level understanding of ethanol-induced stresses and adaptation in E. coli

Understanding ethanol-induced stresses and responses in biofuel-producing bacteria at systems level has significant implications in engineering more efficient biofuel producers. We present a computational study of transcriptomic and genomic data of both ethanol-stressed and ethanol-adapted E. coli cells with computationally predicated ethanol-binding proteins and experimentally identified ethanol tolerance genes. Our analysis suggests: (1) ethanol damages cell wall and membrane integrity, causing increased stresses, particularly reactive oxygen species, which damages DNA and reduces the O2 level; (2) decreased cross-membrane proton gradient from membrane damage, coupled with hypoxia, leads to reduced ATP production by aerobic respiration, driving cells to rely more on fatty acid oxidation, anaerobic respiration and fermentation for ATP production; (3) the reduced ATP generation results in substantially decreased synthesis of macromolecules; (4) ethanol can directly bind 213 proteins including transcription factors, altering their functions; (5) all these changes together induce multiple stress responses, reduced biosynthesis, cell viability and growth; and (6) ethanol-adapted E. coli cells restore the majority of these reduced activities through selection of specific genomic mutations and alteration of stress responses, ultimately restoring normal ATP production, macromolecule biosynthesis, and growth. These new insights into the energy and mass balance will inform design of more ethanol-tolerant strains.

Read the full article here.

SPOTLIGHT ON INDUSTRY: Henrik Hagemann, CustoMem

Henrik Hagemann, CustoMem

What is your background and current job role?

My background is a clash of technical and enterprise, coming with an Imperial College London Biomedical Engineering background (1st class MEng 2015, awarded the only Imperial outstanding achievement medal out of 2200 graduates) where I focused on synthetic biology and biomaterials.

My research focused on synthetic biology tools, as I contributed to a genetic toolkit for biofuels production in thermophilic bacteria (Geobacillus, ACS synbio 2016). As part of Imperial College’s iGEM team in 2014, I co-developed a genetic toolkit for engineering control of bacterial cellulose production in engineered cells (Florea, Hagemann et al PNAS 2016 http://www.pnas.org/content/113/24/E3431). This took me deep into the area of crossing biological membranes (CBM), as the bacterial cellulose fibres are made inside cells and excreted across the cell membrane.

As part of CustoMem, we’re commercialising cellulose based bioadsorbents as a granular water purification product removing contaminants existing biological & chemical processes cannot degrade in industrial water treatment. The granular product retrofits in existing Granular Activated Carbon (GAC) vessels, enables recovery & recycling of contaminants and operates with low energy. The granular product is produced by cell factories using the tools & know-how developed during our research.

My job role as CEO puts me in close contact with collaborators & potential customers around alignment of our tech development with their needs. I also troubleshoot the technical challenges, fundraise, and manage expectations within our team & externally to shareholders.

What Industrial Biotechnology and Bioenergy (IBBE) related project is currently being undertaken by your organisation?

CustoMem is secreting polymers (cellulose) from genetically engineered cell factories, and as such we are currently focusing on 3 IBBE projects:

  • Using the genetic toolkit to further refine the granular product for our chosen contaminant removal
  • Genetic engineering of the cell factories to produce a granular material focused on removal of new contaminants combined with chemical processing of the granular product
  • Optimisation of the genetic pathways for production of granular product with an eye to customise the solution for our customers’ environment

The granular product is sterilised after secretion and production, so there are no living cells in the final product. The granular media is produced to medical grade standards, despite being used in industrial wastewater settings, as an assurance of the sterility of the granular product.

In the future we are looking into collaborating on a number of projects including biologically based recovery of the contaminants captured, remodifying the cell factories to use waste media feedstock, and developing alternative polymers that can be produced biologically with relevance to water treatment.

What do you think the challenges related to this project are in the next 1-5 years?

  • Scale up operation of the granular media in existing GAC hardware
  • Tech alignment with customer needs
  • Regulatory pathway for the products as they will be the first customisable bioadsorbents produced by engineered biology for water purification
  • Large scale recovery and recycling of the contaminants into high value products (elutriation)
  • Price competitiveness, thoroughly assessed at every stage. The key here is taking advantage of the patented biological production genetic toolkit. Currently price competitive with Granular Activated Carbon with a safety factor.
  • Market penetration of granular product
  • Building the infrastructure and supply net for shipping the granular product, regenerating the spent material, elutriation of contaminants and handling the relationship with supply chain network partners.
  • Relocating to larger scale processing labs in the UK
  • Managing large scale bulk material production site

 

How can other CBMNet members help you and your organisation with your research?

For CustoMem, CBMNet is a perfect match in terms of alignment with our tech. As such, CBMNet members can help by collaborating on one of the 3 research projects taking place in our organisation, engage in conversations about complimentary research projects to engage in or as exposure to relevant talent when it comes to recruiting new staff. We’re always hiring, and sometimes tailor roles specifically to a candidate.

There might also be opportunity to invite partners from CBMNet into an industrial research consortium for our current funding proposals for EU, and UK based funding schemes. With the great potential of IBBE and its major challenges when it comes to commercialisation, we’re always more than happy to help with advice about any of the steps required.

SPOTLIGHT ON INDUSTRY: Dr Alexandros Chatgilialoglu, CEO, Remembrane Srl

    

Alexandros Chatgilialoglu, CEO, Remembrane Srl

What is your background and current job role?

In 2010 I co-founded Remembrane srl, of which I am CEO and I am in charge of business development, strategy and sales. Remembrane focuses on membrane lipidomics of in-vitro cultures by developing customized in-vitro lipid supplementation in order to address major culturing issues or boost specific bioprocesses.

I obtained a PhD in Experimental Pathology at the University of Bologna, Italy, on membrane lipidomics of in-vitro cultures. I gained international experience at the Hospital for Sick Children, Toronto, Canada and in Silicon Valley, California, USA, where I was awarded the Certificate in Technology Entrepreneurship at Santa Clara University through a Fulbright fellowship. I experienced the start-up life launch and operations at Lipinutragen S.r.l., a spin-off company of the National Research Council of Bologna, and at SiteOne Therapeutics Inc., a Stanford-based pharmaceutical company. I obtained a Master in Business Administration at Bologna Alma Business School in 2015.

What Industrial Biotechnology and Bioenergy (IBBE) related project is currently being undertaken by your organisation?

Remembrane leads the cell culture technology a step foward, by envisaging the cell membrane network and its lipid composition as a cornerstone of cell physiology. Our current research work is aiming at ameliorating the production process and/or increase the yields of industrial bioproducts such as proteins, viruses, cells, APIs. With this purpose, we have developed customised lipid supplements, called Refeed, able to improve specific biological parameters of cells relevant to industrial bioprocesses.

Our customized lipid supplements are suitable for any in-vitro protocol and cell culture system, ranging from flasks to bioreactors. Targets of our lipid supplements can go from simple microbes such as bacteria and yeasts, to complex insect, plant and mammalian cells. Our supplements can be animal-free, fully synthetic, GMP-grade. Remembrane is fully flexible, with excellent experience and track record, and with a valuable internal database on multiple cell culture systems.

What do you think the challenges related to this project are in the next 1-5 years?

In the next few years Remembrane’s objective is to obtain multiple proof of concepts in different applications of industrial biotechnology. In particular, the supplementation of a multitude of different cell types for the production of a wide variety of relevant bioproducts will be the target of our efforts and collaborations. Moreover, another key challenge will be to standardise our supplement formulations, in order to be able to use them for a cluster of similar applications; this will facilitate the commercialisation of our Refeed products in many different fields of industrial biotechnology.

How can other CBMNet members help you and your organisation with your research?

We are constantly looking for collaborations that will help us in testing our technology on new bioproduction processes, such as new cell types and/or new bioproducts. Therefore, any CBMNet member who is interested in should feel free to contact us to explore new ideas for collaboration. We also welcome the opportunity to explore joint grant applications.

Innovate UK allocated up to £2M for CoBioTech call

ERA CoBioTech – https://www.cobiotech.eu/

It has just been confirmed that Innovate UK have allocated up to £2M to support UK industry partners as part of the current call – Biotechnology for a sustainable bioeconomy. The deadline for submitting pre-proposals is 2nd March 2017, further details are in the call announcement available on the CoBioTech website. If you have any queries about this call please email cobiotech@bbsrc.ac.uk

Invista job vacancies

 

Invista vacancies

At INVISTA, you won’t just be an employee. You’ll be part of a team that works hard every day to support innovations in the nylon, spandex, polyester and specialty materials industries. A subsidiary of privately owned Koch Industries, Inc., INVISTA’s global team is spread out across more than 20 countries around the world.

Charles Koch, Koch Industries’ Chairman and CEO, says, “Innovation is facilitated by having the right people in the right roles with the right skills and values.”

We want the right people in the right roles—and we want those people to be fulfilled in their roles. Fulfillment enables employees to realize their full potential—and helps them improve and grow within their career fields.

Invista currently have 6 advertised vacancies:

  • R&D Senior Bioscientist
  • Fermentation Engineer/Scientist
  • Senior Fermentation Scientist/Engineer
  • Senior Biostatistician – Data management, analysis and visualisation
  • Senior Bioinformatician – Metabolic pathway discovery and optimisation
  • Process Engineering Science Leader

More details for each role including how to apply can be found at http://www.invistainternationalcareers.com/location/wilton/

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