Systems Biotechnology Group


Research Focus:

The research group Systems Biotechnology works in the core areas quantitative physiology and manipulation of redox balances with the overall aim of the sustainable production of chemicals and green energy carriers such as H2. We focus on several key classes of organisms: On the one hand we use photoautotrophic cyanobacteria (farmers) to provide redox power and organic carbon, on the other hand we employ metabolically engineered microbes (including heterotrophs) as production organisms (laborers). A third type of cell might come into play to stabilize synthetic consortia (balancers). We use pure cultures, co-cultures and synthetic consortia to achieve our goals for production. Applying Systems Metabolic Engineering to individual cell types following an iterative design-build-test-learn cycle, is a key approach to achieve our aims.

As a consequence, the group rests on four main pillars: (i) Modelling of metabolism (including metabolic flux analysis and genome scale modelling), (ii) analytics (metabolite fingerprinting, quantification, and isotope enrichments), (iii) in-depth physiology using mass-balanced culture techniques and ‘omics characterization, and last but not least (iv) microbial electrochemical technologies (MET) which allows the reversible conversion of electrical energy into biochemical energy to steer metabolism at the push of a button.

To address the diverse needs of the four pillars, the staff is organized in interdisciplinary research teams with a special focus on certain aspects of the pillars.

New concepts for an integrative bio economy: Sustainable Valorization of CO2 and sunlight
This project aims to generate a sustainable resource platform on the basis of CO2 driven by light energy from sunlight. Several target compounds and reactor platforms are considered and a comparison of state of the art biotechnological- and heterogeneous catalysis is performed. Target molecules include 4-Hydroxyprolin, methane, methanol, oxalic and tartaric acid.


Funded by Freistaat Sachsen

Diese Maßnahme wird mitfinanziert mit Steuermitteln auf Grundlage des von den Abgeordneten des Sächsischen Landtags beschlossenen Haushalts.

(This project is co-financed by means of taxation based on the budget adopted by the representatives of the Landtag of Saxony.)

How do sponges and bacteria together maintain productivity on coral reefs?
Integrating invertebrate biology, microbiology, genomics and metabolomics, this project aims to listen in on conversations between a Great Barrier Reef sponge and its bacterial symbionts. Coral reefs thrive in nutrient-poor tropical seas by relying on efficient retention and recycling of essential elements, and marine sponges are proving critically important in this role. They achieve this by cooperating with metabolically diverse bacterial symbionts via mechanisms that are largely unknown. Using the first and most advanced genome-enabled sponge in the world, this project seeks to reveal genomic and metabolic details of the partnership, with potential to inform environmental restoration, pharmaceuticals and biotechnology.

ARC

The project is a collaboration with the Degnan labs at the University of Queensland (Brisbane, Australia) and  funded through the Australian Research Council (DP170102353).

Fluxomics – Quantifying the metabolic phenotype (Higrade 2018)
With the rise of Systems Biology tools in many areas of the life sciences, data on gene expression, protein abundance and metabolite concentrations become readily available, yet the quantification of intracellular reaction rates (fluxes) is still a non-trivial task for many researchers. This course introduces different concepts of metabolic flux analysis in a hands-on format and enable researchers to develop a quantitative description of their organism or consortium of study.

Masterstudiengang Biochemie, Universität Leipzig (Sommersemester)
Modul: "Quantitative Biologie für eine nachhaltige Umwelt- und industrielle Biotechnologie"

Erwerb von Fertigkeiten in der quantitativen Beschreibung biologischer Prozesse. Nachweis der Lernkompetenz durch Berechnung von maximal möglichen Ausbeuten sowohl in Produktionssystemen als auch bei Abbauprozessen und durch Verfolgung von Stoffflüssen. Dies legt die Grundlage zur Beschreibung der Nachhaltigkeit biologischer Systeme.

Hierbei kommen biologische Datensätze und Modellierungsansätze der Systembiologie zum Einsatz. Die Absolventen erlernen sowohl das Erstellen von Modellen einerseits und die Prozessierung der Daten andererseits. Es werden sowohl stöchiometrische als auch thermodynamische Ansätze verfolgt, um unterschiedliche Prozesse in den Bereichen weiße Biotechnologie und Umweltbiotechnologie zu beschreiben.


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LC-MS/MS based proteomics analysis of Synechocystis sp. PCC6803 phenotype in biophotovoltaics

Understanding how Synechocystis behaviours exposing to anodic electron sink plays a central role in quantitative biophotovoltaics research and subsequent rational system engineering. The project aims to apply the lab-established LC-MS/MS methods to quantitatively address the proteome changes steered by the electrode. Two objectives will be focused on in this project, with each of them corresponding to an individual master thesis:

  1. Global proteome analysis focusing on cellular metabolism in response to different working conditions (e.g. light, working electrode potential, etc);
  2. Membrane proteome analysis with the target to identify key redox proteins involved in extracellular electron transfer or transporters responsible for mediator transportation.

CRISPR-based interrupting system (CRISPRi) for Synechocystis sp. PCC6803

This project is aiming to develop the CRISPRi system to targeted interrupt specific protein(s) of Synechocystis to identity its (their) functions involved in the performance of the microorganism in a biophotovoltaics system. The work will be based on a well-established system developed in KTH Sweden (Yao, L., et al. (2016). ACS Synthetic Biology 5(3): 207-212; Yao, L., et al. (2020). Nature Communications 11(1): 1666) and localize it into our lab. Essential strains and plasmids were kindly provided by Prof. Hudson. As a proof-of-concept study, the initial target will be to create a Synechocystis mutant with inducible inhibition of the photosystem II (PSII) protein complex. Different subunits of PSII should be tested and the time-course PSII activity (based on O2 evolution rate and PAM measurement) should be traced after induction.

Gas composition analysis using membrane-inlet mass spectrometry

This project aims for developing a quantitative protocol to trace the gas composition of the medium in BPV reactor. A membrane-inlet mass spectrometry will be used, and oxygen and CO2 are of particular interest in this project. Oxygen evolution rate and CO2 assimilation rate are the key parameters to be determined. The research question involved in this project is how the photosynthetic and carbon assimilation activities of Synechocystis sp PCC6803 are impacted by the anodic electron sink in BPV system.

Quantitative physiology of Synechocystis sp PCC6803 in response to light availability

Synechocystis is an important model organism for Cyanobacteria, which are considered as phototrophic platform organisms in biotechnology. This thesis aims at quantifying intracellular metabolite concentrations in response to light. These metabolites are the building blocks for biotechnological processes based on CO2. It will involve cultivation of microbes, sampling and mass spectrometry. Knowledge in microbial metabolism and a strong interest in quantitative work are desired.

Fluxomics of Cyanobacteria using 13C tracers

This project aims to determine uptake kinetics of isotopic tracers into the metabolism of Synechocystis sp. PCC6803. It will involve cultivation of microbes, sampling and mass spectrometry. A fundamental interest in microbiology and analytics is desired.

Photolysis of water in a bioelectrochemical system as a path to hydrogenporoduction

Hydrogen is considered a key energy carrier of the future. Splitting water into oxygen and hydrogen is a great way to generate H2. In this project we explore the capability of Cyanobacteria to catalyse this process and use an electrochemical system to separate H2. Being a fundamental research project, creativity and interest in electrochemical technology as well as microbiology are paramount.