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 K-mer methods in Bioinformatics

Recent advances in genetic engineering and genome editing open up new avenues for metabolic engineering and its manifold biotechnological applications. Current inexpensive DNA sequencing technologies allow to keep track of the genomes of the (evolving) recombinant host organisms.

In sequence-based bioinformatics, traditional methods (computationally expensive mapping and alignment of sequenced DNA fragments to genomes) are being replaced by so-called k-mer based methods, which can be much more efficient than traditional methods. In this lecture, we will give an overview of recent developments in this field and discuss applications such as finding strcutural variants in genomes, detecting hybrid DNA, or gene expression analysis.


Pharmaceutical Biotechnology

Pharmaceutical Biotechnology is not only a buzz word in pharmaceutical and engineering sciences, it is already established as a new promissing field of drug discovery and development. Today, the majority of new drugs entering the market and clinics are not only low molecular drugs anymore, we can see a constant trend for so called recombinant therapeutic proteins. These proteins can not be handeled in the classical way because they show different chemical and physical properties. Starting from biopharmaceutical problems like stability in non biological liquids, restricted stability, the tendency for unfolding and loosing activity to sophisticated concepts for drug formulation, and drug targeting to the site of interest in the body. To name some important issues, in this lecture series we address actual research and application questions for recombinant therapeutic proteins to illustrate challenges and beauty of this important class of drugs. Important examples are insulin, its mutein analogs, erythropoetin, follitropin and new DNA and protein based vaccines.



The lectures are intended to provide a basic grounding in absorption metabolism and toxicity of drugs and other foreign compounds (xenobiotics) in human body.

The lecture 1 will present basic molecular aspects determining absorption and elimination of xenobiotics. Basic physicochemical parameters will be explained (logP, total polar surface area, etc.) The lecture will also explain the idea of the therapeutic window to outline how both efficacy and toxicity are dependent on drug concentration, which is in turn linked to the rate of drug removal from the system. Biological systems actively eliminate small xenobiotic molecules and how quickly this happens is a strong determinate of treatment outcome.

Lecture 2 will to put the metabolism of drugs in the broader field of toher biological processes. Human metabolizing enzymes modify xenobiotics and couple them with endogenous molecules, inactivate them and facilitate their elimination from the organism. Drugs fit also into this category and are treated by biological systems as foreing and unwelcome.

Lecture 3 outlines how human metabolizing systems catalyze biotransformation of xenobtiotics. The basic concepts of phase I, II, III will e provided. Pahse I, the initial, mainly oxidative, phase of metabolism, begins the process of the conversion of lipophilic drugs to easily excreted water - soluble metabolites. The remarkable flexibility and capability of these oxidative enzymes will be presented as well as the mechanisms and results of their inhibition and induction. Especially the inhibition of drug-metabolizing systems will be shown as mechanisms able to cause life - threatening drug accumulation in a very short space of time.

Lecture 4 reveals the mechanisms whereby the presence of some drugs can induce a massive adaptive increase in the metabolizing capability of cytochrome P450s. The threat to clinical drug efficacy posed by the resulting acceleration of drug removal from the body is outlined in a number of drug classes. By contrast, the inhibition of drug-metabolizing systems may cause life-threatening drug accumulation in a very short space of time. The mechanisms of cytochrome P450 inhibition are explained in the context of the main pharmacological features of enzyme inhibition.

Lecture 5 explains Phase II of drug metabolism - the processes of conjugation - which can either act as companion processes for oxidative metabolism, or eliminate drugs in their own right. In conjugative metabolisms, hydrophilic molecules are either attached directly to drugs or oxidized metabolites with the object of increasing their water solubility and molecule weight. This process, is orchestrated with Phase III efflux pump systems. These transmembrane transporters facilitates the removal of the metabolites from cells to blood stream and then to the urine and the bile. The factors that may modulate drug-metabolizing processes, such as genetic polymorphisms, age, gender, diet, alcohol intake and disease will be presented. The lecture will explain also some of the toxicological consequences of xenobiotic metabolims. The roles of cytochrome P450s in the origins of revesible and irreversible toxic effects on the cells will be discussed. At the end of the lecture, there is a brief discussion of the role of drug metabolism in the commercial development of new therapeutic agents. Basic computer (in silico) methods used in drug design will be presented.


Natural Product Biotechnology

Nature has proven to be a valuable source in the search for new medicines. The plethora of different bioactive compounds seems to be infinite, but at the same time amounts produced in nature are low and contain impurities. Traditional organic synthesis strategies can replace isolation from natural sources, but is often laborious and economically not feasible due to the complexity of the compounds of interest. Biotechnological approaches offer possibilities to use microbial host organisms for the production of natural products. This enables higher availabitity, but also a continuous supply and less complex isolation procedures. By assembling multi-step pathways into host organisms, products can be synthesized from sustainable and cheap substrates. In addition, enzymes from different origin can be combined and used to synthesize new bioactive compounds, which do not exist in nature. This lecture will focus on the possibilities and limitations of the use of recombinant host organsims for bioactive compounds and will address recent examples and trends in the field of natural product biotechnology.


Pharmaceutical Technology I

Development of paediatric drug formulations


Pharmaceutical Technology II

Formulation Strategies for Poorly Water Soluble Drugs

The low aqueous solubility of novel active pharmaceutical ingredients is one of the major challenges pharmacists have been facing for more than 35 years. Since then several formulation strategies have been developped, which all have advantages but also limitations.

The presentation covers the physical reasons as there are particularly low crystal lattice energy as well as high lipophilicity as main reasons for low aqueous solubility. This requires different formulation strategies like "emulsifying systems", "solid dispersions", "nano particles" as well as "co-crystals" in order to increase the oral bioavailability. These concepts are discussed in detail while market products are mentioned and actual research trends are debated.

Enzymes in the Pharmaceutical Industry

Enzymes play an important role in modern drug discovery, development and manufacturing. The lecture will give an overview and provide examples for applications of Biocatalysis in the pharmaceutical industry. In drug discovery enzymes can be used as tools to study metabolism at early stages to prioritize chemotypes or to selectively modify existing drug candidates or study the SAR (e.g. during hit to lead optimization), including natural products. During development and scale-up synthesis enzymes are used to provide chiral building blocks and finally more and more enzymes are also used in the production process, either for intermediates or even the final API. Advantages and drawbacks will be discussed.


Fundamentals of Protein Chemistry

The lecture provides insights in fundamentals of protein chemistry with a special focus on amino acid  / peptide chemistry and protein folding. This is necessary to work with recombinant proteins, as well as to better understand their industrial production, quality assurance and applications as biocatalysts.

Metabolic Engineering

Plant natural products (PNPs) are unique in that they represent a vast array of different structural features, ranging from relatively simple molecules to very complex ones. Given the fact that many plant secondary metabolites exhibit profound biological activity, they are frequently used as fragrances and flavors, medicines, as well as industrial chemicals. As the intricate structures of PNPs often cannot be mimicked by chemical synthesis, the original plant providers constitute the sole source for their industrial, large-scale production. However, sufficient supply is not guaranteed for all molecules of interest, making the development of alternative production systems a priority. Modern techniques, such as genome mining and thorough biochemical analysis, have helped us gain preliminary understanding of the enzymatic formation of the valuable ingredients in planta. Herein, we review recent advances in the application of biocatalytical processes, facilitating generation of complex PNPs through utilization of plant-derived specific enzymes and combinatorial biochemistry. We further evaluate the options of employing heterologous organisms harboring PNP biosynthetic pathways for the production of secondary metabolites of interest.


The presentations of the lectures can be found in the Moodle Workspace.


Practical courses

A lab coat and protective goggles are mandatory for taking part in the courses.


PDF Herstellung von Mikrokapseln
PDF Production of Microcapsules (english version)
PDF Peptidmustercharakterisierung mittels HPLC; Selektive Spaltung von Insulin
PDF Isolation and Thin-Layer chromatographic separation of carotinoids from different types of paprika powder