Themes & Courses

The themes of ULLA summer school 2021 are primarily focused on topics brought to the fore by the ongoing pandemic. The courses are arranged by teachers and researchers in the ULLA network. See important dates here & Stay tuned for updates!

ULLA laptop theme and courses

Themes & COURSES

Advanced therapy medicinal products

Antiviral drug discovery

Diagnostic tools and principles

Drug design and development of anti-infectives

Formulation and delivery of macromolecules

General skills

Innovation and entrepreneurship

Pharmaceutical biotechnology

Safety and efficacy of vaccines

Vaccine development

Advances in 3D printing of pharmaceuticals

The proposed course will give inside into the new advances regarding printed technologies in the pharmaceutical field. During the course, the participants will get familiar with the most common printing techniques used to produce medical devices and dosage forms. The technicalities (formulation design, printing challenges, characterization techniques) regarding each printing technique would be discussed in the interactive manner. 

The students will actively participate during the online course by doing scientific ‘battles’, answering the ‘Millionaire’ questions and working in a groups to make a ‘tender’. The students will also get hands-on experience by designing their pharmaceutical dosage forms in the computer-aided design software (Tinkercad) by working on a case study. Before the online course, the participant will get a short video (made by the organizer) to have a smooth start during a course.

Course level

  • Advanced

Course leader

  • Natalja Genina, University of Copenhagen

Theme

  • Advanced therapy medicinal products

A hands-on introduction into computational medicinal chemistry

This course offers insight and experience in the molecular modeling tools that enable computer-aided drug design (CADD). As we have seen in 2020 with respect to covid-19 related research, an overwhelming amount data can be produced that can be used as premise for CADD studies. For example, genomics gives valuable information about potential drug targets and the structures of many target proteins are being determined using X-Ray analysis and NMR techniques.

Furthermore, (high-throughput) screening results in massive amounts of data that reveal the molecular properties of the ligands that are able to have interaction with the drug targets.

During this course you will learn to

  • Search target-annotated chemical databases for ligand information and bioactivity data
  • Derive essential features for target-binding based on ligand structures
  • Search protein-structure databases
  • Analyze protein-ligand complexes
  • Explain the effects of site-directed mutations on ligand binding
  • Use protein-ligand interaction analysis to perform docking studies
  • And (if necessary for your protein target) create a homology model

Course level

  • Basic

Course leaders

  • Iwan de Esch, Vrije Universiteit Amsterdam (VUA)
  • Jacqueline van Muijlwijk, Vrije Universiteit Amsterdam (VUA)

Theme

  • Drug design and development of anti-infectives

Applications of chemography

Chemography, or the art of navigating chemical space, can be done using the tool ChemGPS-NP. With the 'maps' retrieved, rapid assessment and comparison of large sets of molecules, evaluation of chemical similarity, and prediction of biological activities can be made - even on entirely hypothetical molecules.

This course explores various uses of chemography and introduces general concepts of analysis using available anti-viral chemistry data.

Course level

  • Basic

Course leader

  • Anders Backlund, Dep. of Pharmaceutical Biosciences, Uppsala University

Theme

  • Antiviral drug discovery

Computational Chemical Biology

Pharmaceutical science is changing; while perhaps not a paradigm shift, the influence and catalytic effect of data science on drug discovery cannot be denied. Scientific data is becoming public and even open access. Moreover, better computing capabilities and more data make it easier to use prior data to improve ongoing work.  

Chemical Biology explores biology via chemical tools. In practice this means that the molecular interaction space of protein targets is probed. Computational Chemical Biology is the computational addition to these goals and is located in between the fields of medicinal chemistry, cheminformatics, bioinformatics, and computational biology. This course consists of bio and cheminformatic approaches which are coupled to structure-based methods using crystal structures. Herein students learn to computationally analyze protein sequences as well as ‘small molecules’, and ultimately model interactions between them using publicly accessible databases and state of the art tools.

The three hours will be used for the theory. Theory will be explained in the form of (online) lectures. At the end of the course materials for hands on exercises will be distributed to the students.

Course level

  • Basic. Understanding of molecules, proteins, and binding is required at the level of a BSc student.

Course leader

  • Gerard van Westen, LACDR, Leiden University

Theme

  • Drug design and development of anti-infectives

Computer-Aided Drug Design

Computer-Aided Drug Design (CADD) is a common approach in medicinal chemistry projects aimed at finding new hits for a given target or in lead optimization campaign.

The fundamentals to understand and exploit many CADD tools often reside in complex equations for energy estimation and geometry optimization of molecular models. Medicinal chemists demand graphical outputs to focus their attention on chemical interpretation, but sometimes a careful consideration of numerical recipes underlying these outputs helps to provide a more realistic sight to CADD predictions or explanations.

This course will deal with the theoretical aspects and the applications of CADD. The theory of force fields, docking methods, and commonly applied computational strategies (i.e. virtual screening methods) and their application to drug design will be presented and discussed.

Course level

  • Basic. Prior knowledge of the Basic concepts of medicinal and physical chemistry is required.

Course leader

  • Alessio Lodola, Department of Food and Drug, University of Parma

Theme

  • Drug design and development of anti-infectives

Crossing the barrier: bringing the biologics revolution to the brain

The use of biologicals (mainly monoclonal antibodies (mAbs)) in indications such as oncology, autoimmune diseases and inflammatory diseases has revolutionized the highly specific treatment of many global acute and chronic conditions. However, the same revolution of using biologicals for brain disorders has not materialized. The main reason is the highly restricted access for biologicals to their brain targets by the presence of different central nervous system (CNS) barriers, including the blood-brain barrier (BBB).

In its simplest description, the BBB is formed and organized by specialized cells that tightly control the movement of various substances in and out of the brain. The limited penetration of antibodies across the BBB results in an estimated level of 0.01 - 0.1 % of circulating antibodies reaching the brain at steady-state concentration. In fact, this holds not only true for large biologics, as also access for small molecules to the CNS is severely restricted (it is estimated that 98 % of small molecules do not adequately cross the CNS barriers either).

This summer course will cover the basic aspects of the BBB, evaluate the available in vitro models to predict delivery over the BBB and discuss available and future technologies and methods to enhance drug delivery to the brain.

Corse Level

  • Basic

Course leader

  • Maarten Dewilde, KU Leuven

Theme

  • Pharmaceutical biotechnology

Hit finding in Medicinal Chemistry

In drug discovery and development, hit finding is the key activity that connects biology and chemistry, by identifying molecules that interact with the biological target (often a protein) in such a way that it modulates the activity of the biomolecule and change cellular responses and (patho-)physiology. The identified hit molecules are the premise for intensive chemistry-based hit exploration and optimization studies.

In this basic medicinal chemistry course, hit finding approaches and technologies will be discussed. We will discuss how to select promising biological targets and list various frequently used assay formats to measure biological activity. We will also discuss different kinds of screening libraries and various ways to explore and optimize (early) hit structures. We will also discuss intellectual property and the role of patents in assuring the identified hits and leads can be progressed towards clinical candidates.

Corse Level

  • Basic

Course leader

  • Iwan de Esch, Vrije Universiteit Amsterdam

Theme

  • Drug design and development of anti-infectives

How can antiviral drugs reach the brain?

The brain is generally protected from viruses by the barriers of the central nervous system (CNS). Yet, the number of CNS viral infections each year is greater than all bacterial, fungal, and protozoa infections combined, representing a significant burden to human health worldwide. In spite of the fact that antiviral drug development has a steep rising curve, the current arsenal of antiviral drugs has limited CNS efficacy.

This short course will give the participants perspectives on the methods and hurdles of drug delivery to the brain by an introduction to basic principles and methods for assessment of brain drug exposure, and will give advice on study design for evaluation of brain drug delivery including novel antiviral drug candidates. Lectures will be interactive with discussion points for the participants to increase the learning outcome.

Course level

  • Basic

Course leader

  • Irena Loryan, Dep. of Pharmacy, Uppsala University

Theme

  • Antiviral drug discovery

Modern tools for pharmaceutical analysis – sample preparation and separation formats

The course will introduce the students to modern tools for pharmaceutical analysis with an emphasis on advanced liquid chromatographic techniques as well as methods exploiting the microfluidic format. These approaches offer new ways to perform bioanalytical procedures for pharmaceutically relevant problems.

The first part of the course will introduce state-of-the-art liquid chromatographic techniques and focus on novel chromatographic support materials from a fundamental point of view. An overview of methods that allow evaluating and improving the performance of these materials will be given. Subsequently, method development will be reviewed based on fundamental principles. The use of column switching techniques will be introduced to approach method development in a generic way.

In the second part, the students will hear about microfluidic formats to perform sample preparation and separation for applications in the pharmaceutical sciences. We will discuss advantages, possibilities and challenges of this format and see examples of how standard approaches can be improved or enhanced in the microchip format. Applications examples include chips to perform extraction of drug metabolites, chips including enzyme reactors for metabolism studies, chips for hydrogen-deuterium exchange to elucidate protein structure, chips as front-ends for small angle X-scattering to investigate protein structure, separation systems on chip, and coupling of chip devices to mass spectrometric detection.

Course level

  • Advanced. Prior basic knowledge on chromatographic separations is required.

Course leader

  • Jörg P. Kutter, University of Copenhagen

Theme

  • General skills

Personalized dosing of antimicrobials in special patient populations

The aim of this course is to provide an overview of current insights in antimicrobial dosing in special patient populations in a hospital setting.  As the antimicrobial drug development pipeline runs dry, and (Gram-negative) bacterial resistance is increasing, appropriate use of antimicrobials has never been more important than today.

Next to correct drug choice, appropriate treatment duration and rapid de-escalation, a lot of research is invested in establishing adequate dosing. Patients suffering from severe illness due to bacterial or fungal infection, such as critically ill, burns, pregnant women, neonates, transplant recipients and patients with hematological disease are particularly vulnerable. Typically, in these patient populations, alteration in pharmacokinetics (PK) is observed, leading to antimicrobial under- or overexposure and hence are at risk for altered drug response (therapeutic failure or toxicity).

During the last decade, many observational PK studies have been published documenting (altered) exposure and PK. More recently, population PK modelling and simulation allowed to define alternative dosing regimens (including therapeutic drug monitoring) leading to better target attainment and hence potentially to a better clinical outcome and less bacterial resistance.

The course is organized in two parts, a (90 up to 120 min) introduction followed by a (60-90 min) interactive case-based discussion.

After completing this course, the participants will have an overview of

  • Current challenges in treatment of bacterial infections
  • Key-elements of correct antimicrobial prescribing
  • PK alterations in special patient populations, and clinical consequences
  • the value of pharmacometrics in informing optimal dosing, aiming at improved target attainment
  • Strategies to improve antimicrobial exposure
    • Stratified dosing
    • Personalised dosing (Model-based therapeutic drug monitoring)
  • Important steps to take in the near future, including implementation aspects

Course level

  • Basic. Prior basic knowledge on on antimicrobials, infectious diseases and pharmacokinetics is required.

Course leaders

  • Isabel Spriet, Dep. of Pharmaceutical and Pharmacological Sciences, KU Leuven
  • Erwin Dreesen, Dep. of Pharmaceutical and Pharmacological Sciences, KU Leuven

Theme

  • Drug design and development of anti-infectives

Selected recent advances in experimental testing

The objective of these courses is to propose 3 scientific fields in which methods have been adapted to the scientific issues. It will also address how alternative methods have been integrated to propose mechanisms of action of xenobiotics.

  • Course 1  The recent progress in animal models of depression
  • Course 2  Assessment of cardiac function: from animal models to iPS cells
  • Course 3  How alternative tests have replaced in vivo tests to measure skin allergy

Course level

  • Advanced

Course leader

  • Saadia Kerdine-Römer, Faculté de Pharmacie, Paris-Sud University

Theme

  • Pharmaceutical biotechnology, Drug design and development of anti-infectives

Therapeutic anti-virus antibodies, where are we?

This course proposes to review the ways in which the main classes of therapeutic antibodies are manufactured for industrial production, and then to focus on the production of antibodies directed against viruses: from the design (according to the target, desired mode of action according to the pathogen) to the production method (polyclonal/monoclonal antibodies, full length antibody, antibody fragments, bispecific antibody, armed antibody).

It will review the anti-viral antibodies currently on the market and also the most advanced antibodies in development.

Course level

  • Basic

Course leader

  • Isabelle Turbica, Paris Saclay University

Theme

  • Pharmaceutical biotechnology, Drug design and development of anti-infectives

Adjuvant therapeutical approaches to fight antimicrobial resistance

The course will be based on the medicinal chemistry of innovative therapeutic agents for the fight of bacterial infections. The first part of the course will be dedicated to a short introduction of one of the most threatening insults to public health nowadays, that is antimicrobial resistance (AMR). How AMR affects public health, both under the clinical and socio-economical point of view, will be explained and commented with the help of epidemiological and socio-economical data.

After this introductory part, the state of the art of the current therapeutic arsenal will be described, with particular emphasis on the most recent FDA/EMA approved drugs and a critical comment on the reasons that have made the antibacterial drug discovery as a neglected research area.

Then, the main mechanisms of bacterial resistance will be illustrated, with a brief description of the most innovative strategies to counteract AMR. In this context, a broad deepening will be dedicated to the exploitation of the so called “non-essential” targets as novel strategies to fight bacterial resistance.

The course will be focused on the medicinal chemistry aspects lining up the design and synthesis of efflux pumps inhibitors, biofilm disruptors and inhibitors of metabolic pathways which are dispensable during bacterial life cycle but become indispensable for bacterial colonization and infection persistence. In these regards, focused case studies will be reported and commented.

Course level

  • Basic

Course leader

  • Pieroni Marco, Institution: University of Parma

Theme

  • Drug design and development of anti-infectives

Inhalation route for local and systemic delivery of biological drugs

Biopharmaceuticals have changed radically the pharmaceutical sector and are going to dominate the market in the future. However, up to now the use of routes for delivery alternative to parenteral administration has somewhat limited their successful application to severe illnesses and hospital use. The application of safe and efficient route of delivery could open new opportunities and application to these potent drugs.

The airways epithelia have emerged as a safe and efficient absorption route for peptide and proteins and could represent the ideal solution for non-invasive biopharmaceutical delivery. Nasal route has been already exploited for delivery of peptides and some products have already been introduced on the market. Pulmonary administration of insulin has been the first scientific breakthrough in this sense for lower airways demonstrating the feasibility of such an approach.

This short course will take in consideration some of the aspects related to the design, development and characterization of biological drug formulations to be administered to the airways with particular focus on the pro and cons of selecting liquid or solid formulation and the matching of a suitable device for drug administration. The course will address in particular the technological aspects related to drug delivery systems and platforms for these administration route. Some specific applications such as vaccination and nose-to-brain delivery will be emphasized.

Course level

  • Advanced

Course leader

  • Ruggero Bettini, Food and Drug Department, University of Parma

Theme

  • Formulation and delivery of macromolecules

Innovative strategies for the production of protein therapeutics in bacteria and their chemical modifications

Protein therapeutics are emerging as the treatment of choice for several conditions, and their use is predicted to increase significantly in the near future. Mammalian cell lines allow for post-translational modifications similar – but not identical – to human proteins and are the production hosts for around 70% of currently approved biopharmaceuticals.

A significant number of protein therapeutics, however, are produced in bacteria, particularly in Escherichia coli, a much cheaper option compared to mammalian cell lines. E. coli cannot carry out most post-translational modifications, thus hindering the therapeutic use of bacteria-produced proteins when these modifications are crucial for pharmacological activity or pharmacokinetics.

Novel approaches, ranging from the engineering of E. coli strains to the chemical modification of purified proteins, have the potential to overcome these limits. The course will first focus on novel aspects of the production of protein therapeutics in bacteria.

The second part of the course will focus on the PEGylation of protein therapeutics and other chemical strategies to improve pharmacokinetics and stability. The discussion will take advantage of examples of proteins studied in our laboratory and case studies of protein therapeutics already on the market.

Course level

  • Advanced. Prior basic knowledge of Chemistry, Biochemistry and Molecular Biology is required.

Course leader

  • Stefano Bruno, University of Parma

Theme

  • Pharmaceutical biotechnology

QM/MM simulations to model enzyme-catalysed reactions: a handbook for medicinal chemists

The quantum mechanics/molecular mechanics (QM/MM) hybrid technique is an important computational method to investigate and characterize chemical reactions occurring in enzymes. An in-depth comprehension of the mechanism of enzyme-catalysed reactions is of critical importance to support and assist the design and development of novel compounds targeting residues involved in the catalytic process.

While experiments alone may not be sufficient to elucidate the mechanisms of enzymes-catalysed reactions, molecular modelling and QM-based simulations, also thank to the current advances in computer power, are gaining an increasingly important role in providing models that can help the interpretation of experimental data or also suggest and drive new experiments.

In this course, some current computational techniques applied to model enzyme-catalysed reactions will be presented. In particular, practical issues that are of critical importance, such as the choice of the method or the preparation of the protein model, will be thoroughly discussed. Examples from the literature showing and discussing the application of QM/MM simulations in the field of medicinal chemistry will be presented, with a particular focus on the case studies of SARS-CoV2 protease and of hydrolases involved in the regulation of inflammatory states.

Course level

  • Advanced. Prior knowledge of the main modelling techniques is desirable.

Course leader

  • Laura Scalvini, University of Parma

Theme

  • Drug design and development of anti-infectives, General skills

High Content imaging for drug discovery: Insights from assay design to primary models

This course describes the steps, processes and approaches needed for drug discovery with a focus on high content screening. Through lectures and interactive workshops (when possible), participants will learn about current drug discovery techniques, from assay development to model selection.

Aspects of clinical testing and precision medicine using high content imaging will also be addressed.At the end of the course, participants should have a good overview and understanding of how high content imaging can aid drug discovery efforts, allowing them to pinpoint potential career directions for their own scientific paths.

The main blocks of the course include:

  1. General screening considerations
  2. Models for screening (2D, 3D and Primary cells)
  3. Image-based strategies for screening (Unbiased assays (Cell Painting) and Biology-directed assays)
  4. Image and Data Analysis (Traditional approaches, AI guided, Data storage considerations, Analysis methods suitable for large datasets (eg KNIME, R, Orange) and Data visualization)
  5. Target identification for phenotypic screens and follow-up (Chemical Proteomics and target ID, Genetic approaches and Transcriptomics)

For the current focus on anti-viral research, examples of drug discovery campaigns and efforts to identify anti-SARS-CoV-2 and genera anti-viral drugs will be shown.

Course level

  • Basic

Course leader

  • Jordi Carreras-Puigvert, Pharmaceutical Biosciences, Uppsala University

Theme

  • Antiviral drug discovery, Drug design and development of anti-infectives

Viral vectors and gene therapy: turning infectious viruses into efficient vehicles to halt and cure genetic disorders

More than 50 years ago the idea that the introduction of exogenous genetic material could serve as an effective treatment for inherited disorders was hypothesized by visionary scientists. Initially, this strategy was envisioned to provide a correct, functional version of a gene to replace a non-functional gene that is the underlying cause of the disease the patient is suffering from.

Theoretically ‘gene therapy’ offers the potential to provide a durable and possibly even curative clinical benefit for the patient with a single treatment. Gene therapy has evolved from science fiction into clinical reality with several gene therapeutic products reaching the market in the past few years providing new treatment options for otherwise untreatable patients in multiple fields of medicine.

We now live in a world where previously untreatable diseases such as Spinal Muscular Atrophy Type I, sickle cell disease, ADA-SCID, and other can be cured or at least halted with single intravenous injections of gene therapy vectors or vector corrected cells.

In the years to come, gene and cell therapy (and ATMPs in general) will become an intrinsic part of our standard treatment armamentarium for human disease. 

In this lecture, I will discuss some of the technologies underpinning the silent revolution of the past few decades, I will review the critical discoveries and milestones in the development of gene therapies, and discuss some of the success stories, and where challenges still lie.  In addition, we will touch upon the current portfolio of gene therapeutic tools, and frame outstanding challenges (manufacturing, biosafety, payment models, ethics). Finally, I will provide insight in some gene therapeutic ATMPs currently available on the market.

Course level

  • Basic

Course leader

  • Rik Gijsbers, KU Leuven, Belgium

Theme

  • Advanced therapy medicinal products

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Anti-infective drugs: Past, Present and Future Directions

Anti-infective therapies are a pillar of modern medicine, and have significantly benefited society since their development over the last century. However, the rise of antimicrobial resistance and new pathogens provides a significant challenge to these foundations.

This course will provide an introduction into anti-infective small molecule therapeutics (including antibiotics and antivirals). Current classes of antibiotics and antiviral drugs will be introduced, focusing on their modes of action and chemical synthesis, whilst also providing the historical context and current societal demand for these important therapeutics. In addition, we will examine current strategies for developing antivirals against SARS-CoV-2. In the final module, we will explore new chemical strategies for identifying anti-infective drugs leads that can be developed towards the clinic.

Course level

  • Advanced, A reasonable background in organic chemistry will be advantageous for this course.

Course leaders

  • Lindon Moodie, Medicinal Chemistry, Uppsala University
    Oscar Verho, Medicinal Chemistry, Uppsala University

Theme

  • Drug design and development of anti-infectives

Introduction to bioprocessing and virtual study visit to Testa Center

The biopharmaceutical market has grown tremendously in the last years with 10-12 of the top 20 drugs by retail sales being biologicals. To produce these drugs in larger quantities, expertise in bioprocessing (growing cells in bio-reactors, harvesting and purification of the product) is necessary. In this introductory course to bioprocessing we have invited specialists from Cytiva (former GE-healthcare) and Testa Center to discuss some of the key elements in the bioprocessing workflow.

In addition to the lecture, we will take you on a virtual study visit to Testa Center. Testa Center is a private-public owned “test bed” for bioprocessing located at the Cytiva site in Uppsala. At Testa Center small (and big) companies and the academia can test, scale up and develop bioprocesses in a factory-like environment and build know-how and value into the projects. Testa Center is also utilized as an education facility for professionals and universities in order for students to meet the increasing need for bioprocess specialists.

Testa Center harbours a unique instrumentation park, not commonly found in university accessible laboratories, with the ability to grow cells at a scale from 1 to 500 L, harvest and purify the products produced.

  • Introduction to some key elements in bioprocessing
  • Study visit to Testa Center

Course level

  • Basic

Course leader

  • Erik Jacobsson, Pharmaceutical Biosciences, Uppsala University

Theme

  • Pharmaceutical biotechnology, General skills

Advanced bioprocessing and virtual study visit to Testa Center

The biopharmaceutical market has grown tremendously in the last years with 10-12 of the top 20 drugs by retail sales being biologicals. To produce these drugs in larger quantities, expertise in bioprocessing (growing cells in bio-reactors, harvesting and purification of the product) is necessary. In this advanced course to bioprocessing we have invited specialists from Cytiva (former GE-healthcare) R&D and Testa Center to discuss and dig deeper into some of the key elements in the bioprocessing workflow.

In addition to the lecture, we will take you on a virtual study visit to Testa Center. Testa Center is a private-public owned “test bed” for bioprocessing located at the Cytiva site in Uppsala. At Testa Center small (and big) companies and the academia can test, scale up and develop bioprocesses in a factory-like environment and build know-how and value into the projects. Testa Center is also utilized as an education facility for professionals and universities in order for students to meet the increasing need for bioprocess specialists.

Testa Center harbours a unique instrumentation park, not commonly found in university accessible laboratories, with the ability to grow cells at a scale from 1 to 500 L, harvest and purify the products produced.

  • Lecture on some key elements in bioprocessing
  • Study visit to Testa Center

Course level

  • Advancerd, some prior knowledge in protein expression and purification is required.

Course leader

  • Erik Jacobsson, Pharmaceutical Biosciences, Uppsala University

Theme

  • Pharmaceutical biotechnology, General skills
Last modified: 2021-04-21