Doctoral Researcher in Saarbrücken bei Helmholtz Zentrum für Infektionsforschung GmbH

Job advertisement no. 185/2023

The department MICA - Anti-infectives from Microbiota, led by Prof. Christine Beemelmanns at the
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken, is offering a position as

Doctoral Researcher (f/m/d)

Project title:

Heterologous expression of cryptic gene clusters and biosynthetic pathway analyses

The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) focusses on identifying and
developing new treatment options for infectious diseases with an emphasis on natural product research.
Especially researchers in the department of Microbial Natural Products are aiming to identify, investigate
and optimize novel natural product based actives, applying diverse approaches and methods mainly from
the field of biotechnology, microbiology, molecular biology and biochemistry. HIPS was jointly started in
August 2009 by the HZI in Braunschweig and Saarland University on Campus Saarbrücken.
In 2015 HIPS moved into a new 4500 m2 research building in which currently 220 international employees
work. HIPS represents the first and only publicly funded extra-university research unit in Germany dedicated
to pharmaceutical research. The Institute collaborates with universities and various industries both
nationally and internationally.

The ERC-funded research project is part of the ERC Starting Grant MORPHEUS, which studies the function

and origin of bacterial natural products and biomolecules involved in the cell differentiation processes and

defense of marine organisms.

The PhD project encompasses several key components and tasks:

1. Genome Mining of Marine Bacterial Genomes and Metagenomics Datasets

o Undertaking genome sequencing efforts to explore (meta)genomes.

o Evaluation of hybrid gene cluster pathway constructs.

2. Heterologous Expression of Small Hybrid Gene Clusters:

o Design of gene constructs for expression in the host(s) of choice.

o Optimizing heterologous expression conditions

3. Metabolomic Analysis of Heterologous Products:

o Utilizing high-resolution mass spectrometry to monitor product production.

o identify products using advanced analytical tools (Collaborating with experts).

4. Manipulation of Gene Clusters and Monitoring of Product Scaffolds:

o E.g. Single point mutations, module exchange

5. Analysis of wild-type producers

o Microbial cultivation techniques

In this project, the successful candidate will contribute to genome sequencing efforts, focusing on identifying

cryptic gene clusters encoded within (meta)genomes. Heterologous expression of selected sequences in

different hosts will be carried out, with subsequent monitoring of product production using high-resolution

mass spectrometry. The biosynthetic pathways expressed heterologously will be tested for substrate scope

and biochemical properties. Simultaneously, wild-type microbial producers will be cultivated and analyzed

to characterize the natural product portfolio. Collaborative efforts will involve using state-of-the-art analytical

tools for product identification.

This multi-faceted approach will enable the candidate to gain expertise in microbial cultivation techniques

and apply advanced molecular biological and analytical tools for the identification of novel natural products.

Qualifications:

Master degree or equivalent in Life Sciences, Biotechnology, Pharmacy Chemistry, or related fields.

Strong hands on experience in laboratory and analytical techniques.

General understanding of molecular biological approaches, chemical and biochemical transformations

Ability to pay attention to details, pursue research independently and work in a goal-oriented manner.

Willingness to work in a plural, collegial, international and interdisciplinary environment.

Excellent English communication skills (written and spoken); very good skills in scientific writing

Disabled persons are given preference in the case of equal professional qualification. The HIPS aims for
professional equality between women and men. The position is suitable for part-time work.

Advantageous for this position:

Experience in next-generation sequence methods/techniques

Experience in DNA isolation, PCR and cloning techniques

Isolation of bacterial strains, microbial cultivation techniques, phylogenomic analyses

We offer:

modern laboratories and state-of-the-art instrumentation

a dynamic and international research environment

extensive further training o