Molecular Medicine

This module aims to develop your skills in information literacy, oral presentation, scientific writing, critical analysis, data analysis, statistics, ethics, research integrity and basic laboratory techniques. These are all skills that support subsequent modules, the laboratory project and dissertation writing, and are also transferable skills useful in many future careers.

The module consists of lectures, tutorials, active (interactive) teaching and group work, followed by taster sessions in various different laboratory techniques.

 Understanding the molecular and cellular pathogenesis of human diseases is critical for developing new strategies for disease prevention, diagnosis, and treatment.



Students will learn about the current field of Molecular Medicine, using relevant examples of specific diseases that are understood at both the molecular and cellular level, and that are the areas of expertise of our teachers. Students will gain knowledge about a spectrum of diseases, ranging from the relatively simple examples that are caused by a single gene defect, to those where a frequent variant of a gene makes a substantial contribution to causing disease, and then on to disorders that share molecular mechanisms but where there is no specific evidence for an inherited genetic susceptibility. These will often include the ultimate 'disorder of the genome', cancer, where the primary defect is the loss of the cell's normal capability to maintain the stability of its own genes. Students will investigate the consequent changes that can drive progression and spread of cancer, and discuss programmed cell death, its failure in cancer and in infectious and autoimmune diseases. The emerging understanding of the role of the microbiome of skin and gut in maintaining human health and how an imbalance in the microbiome may contribute to diseases, including autoimmunity inflammatory diseases and the progression of cancer, will also be explored.



Teaching will be through a combination of lectures and tutorials. To support students' understanding of our teaching and the background literature, we will include discussion of cellular and molecular processes and methods for interfering with the function of specific entities within cells. We will also provide optional extra teaching to provide more background in relevant techniques and molecular processes for students who feel that they would benefit from them.

This module will provide students with a comprehensive understanding of the human immune system and its role in disease. Students will learn about the different components of the immune system and the mechanisms involved in protecting the body against pathogens, and how disruption of these can lead to chronic inflammatory and infectious diseases. Additionally, students will be taught using examples of primary research to illustrate how the immune system is involved in the development and progression of diseases such as cancer, autoimmune disorders, and infectious diseases.

The use of appropriate model systems to study the immune system, including in silico, in vitro and in vivo models, will also be covered in this module. Students will learn about the advantages and limitations of different models and how they can be used to study the immune system in both healthy and diseased states. They will have the opportunity to visit our laboratory facilities and observe demonstrations of these models, and will learn how to apply their knowledge of the immune system to critically evaluate the methods and results of laboratory based and clinical research studies.

Teaching will be through a combination of lectures, tutorials, and discussions, as well as visits to laboratories, clinical research facilities, and clinical departments.

Modern experimental programmes often deliver massive datasets because we are now able to deliver high throughput data economically. This falls principally into high throughput sequencing of RNA and DNA and mass spectrometry of proteins. This information is seldom interpreted from scratch but can be mapped onto the massive data held on public archives. The first of these is the human reference genome. Students will learn how the most significant current nucleic acid  sequencing methods operate and how mass spectrometry is used to analyse the entire protein content of a cell and how the same methods can be adapted to read the phenotype of single cells within a tissue.

Students will learn in computer classes how to map sequence onto genomes and other reference genomes, design PCR reactions, identify previously known and unknown genetic variations from database information. In the field of infectious diseases students will use sequence data to classify pathogens.

Students will learn and experience hands-on, in computer classes, how raw sequence data are analysed. Students will be introduced to the programming language R and will learn to use it to analyse and display data sets. With preconfigured software, students will identify networks of activated genes in human cells and identify resistance genes in pathogens.

Students will discover how chronic diseases, especially those that are common in the aging population have shared features with many overlapping causes and consequently patients are often co-morbid for several disorders. The module will explore how specific disorders have been studied, focussing particularly on the use of model systems to explore the molecular and cellular basis of disease to the point of identifying potential drug targets. Students will learn to assess critically the primary scientific literature that supports the identification of significant pathogenic processes. Areas of focus will be inflammation and inflammatory diseases, metabolic syndrome and its consequences and pathways in neurodegeneration.

The module focuses on the genetic and phenotypic changes that evolving cancer cells commonly undergo as they become more malignant and metastatic and how, if they are 'successful', they significantly influence their environment and the phenotype and behaviour of bystander cells including components of the immune system to favour disease progression. Central to this understanding is our ability to identify the mutations that drive progression in individual cells and the unusual expression of proteins that results from genetic change. If we can identify common driver pathways between individual cancers, then it allows us to improve prognosis and design and apply targeted therapies.

Orally available small molecules are the primary goal of the pharmaceutical industry and in wealthier health systems, agents that need to be continually supplied to treat a chronic condition are the most attractive. Traditionally, the efficacy of drugs in treating human disorders was discovered before the drug's biomolecular target was understood. Recent developments in protein structural analysis and modelling has allowed 'lead' molecules to be selected and optimised for specificity by computer design. Drugs, however, are subject to unpredictable absorbtion, metabolism (which will vary between patients), import into cells, export from cells and excretion. The drug's target molecule can sometimes have an additional, unrecognised function. Small molecules are also likely to interact to an unknown extent with other off-target molecules and activate the metabolism of other drugs causing drug-drug 'interactions' and side effects. A phased programme of drug testing is therefore ethically justified and legally required and as a consequence of failures during testing, the majority of tested drugs are abandoned.

In infectious diseases and in cancer, known efficacious drugs can become non-efficaceous as a result of changes in the target, whether this is a tumour cell or a microbial pathogen. Small molecules can be redesigned at random and tested against known variants or molecules can be re-designed in a computer model to re-target a specific variant. Individual responses to drugs also depend upon the patient's genetics, comorbidities or metabolic state and specific drugs may be effective in one patient but not another.

This module uses seminars to introduce students to the pharmaceutical industry's approach to new drug design.

Students will receive hand-on introduction to computer based molecular docking of small molecules with protein targets. Students will be led through a number of examples of promising,  validated and/or efficacious smal molecule treatments that have been developed in collaborations involving the University of Sheffield. Students will be introduced to programmes of drug testing and of the potential use of genetic profiling to predict drug efficacy.

Re-engineered protein molecules, expressed in bulk in industrial-scale cell culture systems, engineered virus-like particles that can carry corrected human genes, modified-RNA vaccines  and re-programmed immune cells from patients are among the agents categorised as 'biologic' that are currently used to a greater or lesser extent in human therapy.

Fledgling biotech companies (in the 1980s) regarded protein therapeutics as a temporary step towards the development of highly specific small molecule therapies, yet recombinant proteins and particularly, antibodies, remain a hugely important and still growing field of pharmaceutical development. In replacing the failed products of dysfunctional genes or missing cells, protein therapeutics cannot be substituted with small molecules. As antigens for use in vaccines or vectors for expressing the genetic code of a pathogen, biologics are irreplaceable. The specificity of recombinant antibodies to target a disease-related agent can justify their enormous cost, relative to small molecules, when the small moleule therapies fail. The number of recombinant antibody therapeutics is still expanding.. Reprogramming patients' immune cells to target their own cancers is a very promising new approach to destroying incurable aggressive cancers. The module introduces students to all of these therapeutic approaches, how biologics are developed and how they produced. Biologics are generally limited in their global reach because of their physical and chemical instability, their need to be injected often in a hospital environment and their very high cost. The module will discuss how these concerns are being partially addressed.

The module allows students to develop as a research scientist in an area of research fitting the area of their degree and often diectly developing themes from previous teaching.

Students experience the scientific process of hypothesis testing, developing the relevant hands-on skills (in the laboratory) and/or understanding of the experimental process (if a non-laboratory project is chosen).  With supervision, students will learn to analyse results and will eventually formulate their own experiments and have the opportunity to develop new hypotheses.



Students will choose several from an extensive list of individual projects. The list will contain an informative title and include links to an extensive abstract and references that students may explore. Students are expected to meet their candidate supervisors before selecting their projects. Students will be assigned one of their selected projects.



Students carry out an individual 20-week research project and complete three activities for assessment with guidance from their individual supervisor. [1] Students prepare a poster, outlining the scientific background of their project.[2] After several weeks engaged in the project, students will present the background, the hypothesis, their experimental procedures and any results that they might have at this stage. [3] By the end of the project period, students will produce a  dissertation which will include a survey of relevant background knowledge, a clear statement of the hypothesis or hypotheses that the student's work addressed, a report of the methods used, results achieved and a discussion of the implications of the results for the hypothesis and the significance of the results in relation to the field.

[4] A further marked component will consist of an assessment of the student's practical skills and their engagement with the research team during the project.