academic year 2024/2025

A critical piece in drug discovery and development is conducting DMPK (Drug Metabolism and Pharmacokinetics) studies, often referred to as ADME-T (Absorption, Distribution, Metabolism, Elimination, Toxicity). ADME studies are designed to investigate how a chemical (e.g. a drug candidate) is processed by a living organism and how ADME properties could affect its activity. For a drug candidate, "optimizing" ADME properties before clinical investigation is of utmost importance to ensure it is as effective and safe as possible; it is estimated that close to 50% of drug candidates fail because of unacceptable efficacy due to an unfavourable ADME profile. This course aims to provide PhD students engaged in the early drug discovery process awareness about the importance of preclinical ADME investigation, the strategies and the methodologies that assist to achieve efficiency in the hit-to-lead process.

This course aims to provide a comprehensive overview of the design, formulation, preparation, control and regulatory aspects of Advanced Therapy Medicinal Products (ATMPs). In the first part, the regulatory framework and scientific basis of ATMPs will be presented, while the second part of the course will be focused on the formulation and technological aspects as well as the industrial production according to the Good Manufacturing Practice (GMP).

Wine aging is a complex process that significantly enhances the flavor, aroma, and texture of wine. During aging, chemical reactions involving acids, sugars, phenolic compounds, and alcohols occur, leading to the development of new flavors and the softening of tannins. The aging process can take place in various environments, such as oak barrels or bottles, each imparting unique characteristics to the wine. Oak barrels, for instance, add notes of vanilla, spice, and toast, while bottle aging allows for the gradual integration of flavors and the development of tertiary aromas like leather, tobacco, and dried fruit. The duration of aging depends on the type of wine and desired profile, with some wines benefiting from several years of maturation.

The gap between the damaged fragments has to be filled with functional materials that act as a substrate and as a physical three-dimensional microenvironment for inducing the migration and organization of cells from the native tissue. Strarting from biomaterials used in orthopedic applications, tissue engineering as new treatment alternative will be described with scaffolds and cells. Regenerative medicine that want to replace and repair lost or damaged tissues and organs will be the last point discussed. 

Bioorganic chemistry deals with the understanding of biochemical processes and their application for the development of novel organic chemistry tools. Throughout the course, you will gain a basic understanding of bioorganic chemistry: starting from its key concepts, the course will develop through the analogies between organic reactions and biochemical transformations (Biomimetic Chemistry), the catalytic mechanisms of several classes of enzymes, and how some of the effects we observe in enzyme mechanisms can be applied to organic synthesis as well. 

Prerequisites 

Basic knowledge: acid-base theories; principles of chemical kinetics and fundamentals of thermodynamics. 

Knowledge of organic chemistry: structure, properties, and activities of the main functional groups of organic chemistry; fundamentals of stereochemistry.

 !!! WARNING !!! Although the instructor of this course is an organic chemist, this is definitely NOT your typical CHEMISTRY course!

You do not need to be a chemist to appreciate the topics covered in this course. No matter your background, the subject matter is presented in an accessible and engaging way, suitable for everyone, regardless of their expertise in CHEM, BIO, or other fields.

By exploring legends, tales, and small historical gems intertwined with chemistry, we will uncover how individual molecules, primarily of plant origin, have played significant roles in influencing (and sometimes completely altering) the course of human history. Given the nature of the topics, the course will be conducted exclusively in Italian.

Prerequisites
Basic knowledge: how to read a chemical structure

The course will focus on the main lifestyle of microorganisms and its impact and relevance in the context of implantable devices infections.  Explanations about the main features of biofilms, the stages of their formation and development as well as the mechanisms of resistance to antimicrobials and their effects will be also provided. Furthermore, the potential of innovative anti-adhesive coatings on the surfaces of biomedical device-relevant materials for the prevention of biofilm-associated infections will be explored.

In the field of pharmacological research, scientists employ various experimental methods to understand complex biological processes. Two fundamental approaches of this exploration involve the development of "In Vivo" and "In Vitro" studies. These terms represent two distinct experimental complementary contexts with unique advantages, applications, and limitations.

In vitro models represent the first approaches used along the drug discovery process to characterize the activity, efficacy, toxicity, biocompatibility and ADME of new drug candidates giving many information exploitable in the in vivo studies. Moreover in vitro models represent simplified but versatile models of in vivo tissue/organs that help researcher to obtain many results that can also be spend to better plan their in vivo research.

Once a drug candidate demonstrates effectiveness in in vitro experiments, in vivo models can be employed to advance drug development studies. These preclinical studies typically involve the use of animals to evaluate safety, efficacy and delivery of a drug candidate. On the other hand, in vivo models provide some drawbacks like difference in biokinetics parameters or extrapolation of results to human.

The aim of this course is to illustrate to PhD students how to critically choose between in vitro and in vivo studies, to understand their usefulness and to explore their mutual complementarity. During classes, examples of in vitro and in vivo models used nowadays for the development of drug candidates will be addressed. 

A food colorant is “any dye, pigment or substance that can impart color to a food, drug, cosmetic or the human body”. Starting from the FDA definition, the course will be directed to understand the chemistry of food colorants, their properties, including functional properties, their toxicology. Finally, some innovative perspectives will be analyzed following the question “Eating with the eyes is possible?”

Immunotherapy is a cancer treatment that uses the immune system's innate abilities to find and destroy cancer cells. There are several immunotherapy strategies, but they all work by training the immune system to fight cancer. The course will provide an overview of the molecular mechanisms underlying the dynamic connection between the immune system and cancer cells, the latest approaches to harnessing the anti-tumor activities of immune cells (monoclonal antibodies, drug-conjugated antibodies and CAR-T) and the major challenges that remain to be overcome.

Over the past two decades, the field of drug discovery has witnessed a paradigm shift towards innovative approaches for modulating complex biological targets, leading to transformative therapies that deeply impact patients and their families. The traditional R&D landscape, once dominated by small molecules confined to specific property and mechanism spaces, has expanded to embrace a new wave of chemical modalities. These emerging modalities focus on modulating target expression rather than directly affecting target function. Examples include RNA-based therapeutics, protein degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues (MGs), macrocyclic peptides, antibody-drug conjugates (ADCs), and gene therapy. Many of these technologies have matured, achieving clinical success and unlocking new avenues for biopharmaceutical innovation.

This course aims to provide a comprehensive overview of these new chemical modalities in drug discovery, with an emphasis on proximity-based approaches (e.g., PROTACs, MGs, and trivalent or trifunctional molecules), covalent drugs, therapeutic peptides, and ADCs. Key topics include the rational design and development of these modalities, their advantages and challenges compared to conventional small molecules, and their current applications and potential future directions in the field.

The advent of artificial intelligence has changed the tools used by scientists for the prediction of protein structures. This has also marked a dramatic advancement in the de novo design of proteins, enabling the engineering of new proteins with tailored functions. I will present the most recent breakthroughs in experimental protein structure analysis and in computational protein structure predictions, with a focus on protein design and on drug discovery. 

Brain activity can be studied using multiple methods. Some of these methods are non-invasive, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), diffusion tensor imaging (DTI), and electroencephalography (EEG). Other methods are invasive, like physiological recordings of single units and local field potentials using intracranial electrodes. We will examine some studies on their applications in the fields of the placebo effect, vegetative state, and brain-machine interfaces.  

NMR spectroscopy is routinely used to evaluate identity and purity of chemical substances. Most users produce NMR reports based solely on the recording and interpretation of simple 1H and 13C spectra, leaving out information that could be easily recovered with a more in-depth interpretation or with simple additional 1D or 2D NMR experiments. A brief introduction to simple 1D and 2D experiments will be provided, along with instructions for interpreting and reporting NMR data (0.5 CFU). A case study with the complete assignment of the 1H and 13C resonances for a steroid will be presented and discussed (0.5 CFU). 

This short course is targeted at those (biologists but also chemists) who wish to learn the basics and challenges of drug screening on information rich cell based models.

Cell-based assays, because of their advantages in terms of predictability, multiplexing, miniaturization and automation seem the most appealing tool for the high demands and high quality standards of the early stages of the drug-discovery process. Nevertheless,scientists working on assay development for cellular screening still face a variety of challenges. Aspects of assay design ranging from cell type choice, readout selection, standardization, miniaturization, data analysis, will be covered. Moreover, advantages of targeted versus phenotypic assays in drug screening will be discussed. 

Medicines have undergone significant advancements over the past 70 years, with major progress in technology and target selectivity. This course provides an overview of pharmaceutical drugs beyond traditional chemical entities, including biological and biotechnological drugs, as well as cell therapies. The course aims to explain how biotechnological drugs are produced, their methods of administration, clinical applications, and the advantages and disadvantages compared to small-molecule drugs. Additionally, participants will engage in laboratory sessions to produce and purify a biotechnological drug, such as a monoclonal antibody or a pharmaceutical protein.

The course is divided into two parts. The first one will introduce the students to the basics of health economics: demand for health and healthcare, supply of healthcare, market mechanisms, market failures and regulation. The second one will discuss the application of health economics to the pharmaceutical market and will be focused on economics of research and development, regulation and market access (drugs approval, reimbursement, price regulation and procurement).

Image acquisition using laser scanning confocal microscopy (LSCM), commonly referred to as confocal microscopy, has become a daily routine in biomedical research. However, the effective use and full exploitation of the potential of LSCM requires a solid understanding of various aspects of optical fluorescence imaging and laser scanning technology. This course will provide basic knowledge on fluorophores and fluorescent proteins, explain the operational principles of confocal microscopy, and guide PhD students in acquiring high-quality images and performing post-imaging analysis for figure preparation in publications.

Design of Experiments (DoE) consists of a panel of chemometric procedures and algorithms aimed at planning the experimental work in a rational way, which means projecting the experiments in order to acquire the highest amount of high-quality and relevant information while performing the lowest number of experiments, thus reducing the experimental effort. In this scenario, the aim of the course is to introduce the DoE to beginners, providing a simple description of the mathematical principles behind these tools but mainly focusing on practical aspects, real-case application and results interpretation thanks to a large variety of practical examples and real datasets. Together with the theoretical description of the most common designs, a few practical exercises will be proposed and carried out together with the students by means of the open-source software CAT, freely downloadable, in order to provide the students with all the basic knowledge to autonomously apply DoE in their future career. Finally, brief hints to more advanced techniques aimed at investigating more complex or specific problems will be presented to provide the students a wider panorama of the countless opportunities offered by Design of Experiments. 

Immerse yourself in the fascinating world of International Nonproprietary Names (INN), the universal language for pharmaceutical naming. This course, hosted by the Università del Piemonte Orientale—pilot center for the WHO School of INN—offers an introduction to the rules and strategies behind the creation of INNs. Through interactive sessions, participants will review and analyze real-world cases. 

Protein crosstalks as well as protein-ligand interactions play essential roles in many biological processes including signaling pathways, transcriptional regulation and numerous other metabolic reactions. In order to understand the role of such protein interactions in biological processes it is important to investigate the interaction dynamics describing the stoichiometry of the complexes, the binding free energy and their binding cooperativity as inter-molecular communication. These biochemical parameters are complementary to structural biology studies. In particular, the enthalpic and entropic components of the binding free energy directly refer to the mechanistic aspects of the binding and have been widely exploited in drug discovery research pipeline.

The aim of this course is the description of practical and theoretical aspects of biophysical methods used for measuring the stoichiometry and affinity of many protein interactions. In particular, the course will focus on the application potential of the following techniques in the field of biochemistry and  structural biology: i) small-angle X-ray scattering; ii) isothermal titration calorimetry (ITC); iii) differential scanning fluorescence (DSF); iv) surface plasmon resonance (SPR) and v) microscale thermophoresis (MST).

The natural compounds are an endless source of ideas for the discovery of new drugs to treat diseases, and the total synthesis of complex natural products still represents a big challenge for the organic chemist. While many strategies applied to the synthesis of complex natural products are based on the construction of individual rings or fragments of the natural products followed by a unification step, or by the iterative annulation of one ring onto a preexisting ring, an efficient alternative strategy could be represented by the transannular cyclization reactions.

Transannular reactions are defined as “those reactions which lead to the formation of covalent bond between atoms on opposite sides of the ring compound”.1 They usually occur in macrocyclic compounds that, to minimize transannular strain (Prelog strain), are constricted in rigid conformations that force some functional groups to be close to each other.2

This intimacy between functional groups confers entropic advantages “to enable transformations that are otherwise difficult in intermolecular and intramolecular settings”,3 making transannular reactions a highly efficient tool for the construction of complex polycyclic architectures.

Transannular reactions are classified according to the reaction type involved in the cyclization process [Diels-Alder (TADA), ene reaction, [2+2] and other cycloadditions, Michael addition, aldol condensation, Mannich and miscellaneous reaction].4

The transannular cyclisation process is the result of a series of cascade reactions that allow us to obtain a complex polycyclic architecture from an easily accessible macrocyclic compound, representing a shortcut in the synthesis of complex natural products. The entire process can be highly influenced by several factors such as the conformation of the macrocycle and the activation strategy. This course will outline the main features and the applications of transannular ring closure reactions and examples will be given to validate this approach as a versatile, efficient and flexible strategy to access new polycyclic structures on the way to the synthesis of important natural products.

1.  D.C. Harrowven, G. Pattenden Transannular Electrophilic Cyclizations in Comprehensive Organic Synthesis 1991, Volume 3, 379

2.   J.D. Dunitz, V. Prelog Angew. Chem. 1960, 72, 896. R.A. Raphael Proc. Chem. Soc. 1962, 97. 


3. T.T.H. Dao, T. Marmin, Y.L. Dory, Transannular Electrophilic Cyclizations in Comprehensive Organic Synthesis II 2014, Volume 3, 293

4.  A.C. Cope, M.M. Martin, M.A. McKervey Quarterly Reviews, Chemical Society 1966, 119. P.A. Clarke, A.T. Reeder, J. Winn Synthesis 2009, 691. E. Reyes, U. Uria, L. Carrillo, J.L. Vicario Tetrahedron 2014, 70, 9461. 

Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are essential for advancing new treatment strategies. Currently, the most commonly used models are two-dimensional cell cultures derived from primary tumors or bodily fluids. Although these models have contributed valuable insights into cancer biology, they possess significant limitations. To overcome some of these challenges, researchers are increasingly utilizing spheroids, tumor-derived organoids, and microfluidic chips to explore the influence of three-dimensional environments on tumor behavior. Additionally, significant progress has been made in developing animal models, including genetically modified mice and patient-derived xenografts. We will highlight strengths and weaknesses of the available in vitro and in vivo models. 

For PhD students, the prospect of writing their very own scientific research paper may be both exciting and hard. The goal of this course is to provide effective tools to improve writing skills and manuscript writing process.

Public speaking is a skill that can benefit anyone, whether it is for a professional, academic, or personal purpose. However, many people struggle with anxiety, lack of confidence, or poor communication  techniques when they have to speak in front of an audience. This brief course will start from analysing how to overcome these challenges and improve the ability to deliver effective and engaging  presentations. This public speaking course will cover the following topics:

• The basics of public speaking, such as understanding the target audience, planning and organizing the content.

• The techniques of public speaking, such as using appropriate language, voice, gestures, eye contact, and visual aids, and adapting to different situations and feedback.

• The practice of public speaking, such as preparing and rehearsing the speech, managing nervousness and stress, and handling questions and objections.

Public speaking is a skill that anyone can learn, manage and improve and is beneficial not only for professional preparation but it helps increase self-confidence. In other words, students might find it helpful even for more personal aspects in their daily life. 

Cannabis sativa L. is a plant with a huge impact on both a historical, social and scientific point of view. After a long period of prohibition, in recent years we are witnessing a renewed interest in its cultivation and applications in many sectors, including industrial, pharmaceutical, food and cosmetics. However, the confusion surrounding this plant has reached unprecedented levels, and never before has misinformation strayed so far from science.

For the correct use of Cannabis, particularly in the pharmaceutical sector, it is essential to know not only the characteristic cannabinoids of the plant, but also the numerous biosynthesized secondary metabolites, as well as their chemical-physical properties, in view of formulations or isolation from extracts. In addition to this, it is also important to apply the concept of phytoequivalence when the preparations are not monomolecular, and to know the limits and regulations regarding its use.

This course aims to provide the basis of the phytochemistry of C. sativa, highlighting the main molecules of applicative interest, the fundamental processes for their production and, finally, the importance of correct and conscious use of the preparations obtained. 

The interdisciplinary course will provide an overview of the immunomodulatory activity of microbiome and itsimpact on the pathogenesis of human diseases, such as immune-mediated diseases and cancers. Particular attentionwill be given to the study of the dominant members of the skin and gut microbial ecosystem, their spatial distributionamong physical niches and their crucial functions in human health. Potential therapeutic approaches to modulatemicrobiota composition in the contexts of inflammatory disorders and cancer therapy will be also discussed.

The scope of this presentation is to give an overview of the different bioanalytical approaches used to support New Biological Entities (NBE) and Antibody Drug Conjugates (ADC) projects.

Ligand Binding Assays are considered the gold standard for the determination of the concentration of proteins and antibodies in pharmacokinetic (PK) and toxicokinetic (TK) studies (serum, plasma); different approaches will be presented including ELISA, Gyrolab, Mesoscale Discovery (MSD), and SMC technologies.

Immunogenicity risk associated with the development of anti-drug antibodies (ADAs) following administration of biotherapeutics is considered one of the main issues in the development of New Biological Entities. For this reason, different approaches to detect ADA in in-vivo studies will be presented.

LC-MS technique is also emerging as an alternative tool for the determination of the concentration of total Antibody in biological samples. In addition, LC-MS/MS techniques can be employed to support in vivo ADC pharmacokinetics studies: they can be dedicated to the quantitation of the conjugated toxin, detecting the active molecule, after the capture of the entire ADC and enzymatic cleavage of the linker. Moreover, LC-MS/MS methods are used to quantify the unconjugated toxin potentially released from the ADC.

Cell-based assays are playing a crucial role in the development of NBEs. Different approaches based on flow cytometry will be presented for the understanding of the mechanism of action of novel drugs in in-vitro (target internalization) and in-vivo (receptor occupancy) studies.

Finally, an overview of the pharmacokinetic properties of NBE will be provided including the different data analysis approaches used for PK parameters determinations.

The course aims to enrich the theoretical knowledge of statistics and probability with suitable data analysis skills; the course focuses also on data visualization and is based on the free and open source software R.

Formulation step represents a key point in the development of finished pharmaceutical and cosmetic products. The aim of this course is to provide a theoretical and practical overview of formulation approaches and strategies to obtain a successful product.

The advent of immunological therapies against tumors has represented a real revolution in oncological therapy, improving the quality of life and survival of patients.

Despite this, a significant proportion of patients do not respond to therapies or develop toxicities incompatible with the new therapeutic regimens. The myeloid component of the immune system represents a predominant part of tumor-infiltrating leukocytes and their frequency and state of activation has been correlated with both tumor progression and the development of mechanisms of resistance to therapies. These cells are phenotypically heterogeneous, able to dynamically express both tumor-suppressive and tumor-promoting effects, significantly contributing to resistance to cancer treatments, in particular to immunotherapies. The course of study will discuss the interaction between different myeloid subtypes and other cellular and non-cellular components of tumors, highlighting the mechanisms by which these cells promote tumor progression and resistance to therapies.

The course aims to present recent developments in the design of targeting and drug delivery strategies for biological and biotechnological drugs using nanoparticulate systems. Smart nanocarriers composed of organic materials (polymeric micelles and vesicles, liposomes, dendrimers, and hydrogels) and inorganic materials (quantum dots, gold nanoparticles, and mesoporous silica nanoparticles) will be described.