MED-MM2CF
Metabolism, Transport and Motion
Course infoSchedule
Course moduleMED-MM2CF
Credits (ECTS)3.5
CategoryMA (Master)
Language of instructionEnglish
Offered byRadboud University; Faculty of Medical Sciences; Molecular Mechanisms of Disease;
Lecturer(s)
Examiner
dr. M.M.P. Zegers, PhD
Other course modules lecturer
Lecturer
dr. M.M.P. Zegers, PhD
Other course modules lecturer
Contactperson for the course
dr. M.M.P. Zegers, PhD
Other course modules lecturer
Academic year2018
Period
3  (29/10/2018 to 25/08/2019)
Starting block
3
Course mode
full-time
Remarks-
Registration using OSIRISYes
Course open to students from other facultiesNo
Pre-registrationNo
Waiting listNo
Placement procedure-
Aims

This course will make you familiar with defects in energy metabolism and transport and with the biomedical research towards the molecular mechanisms, diagnosis, treatment and prevention of these diseases. Focus is on the molecular aspects of certain disorders of energy metabolism (eg. mitochondrial and lysosomal disorders) and transport (eg. disorders of renal water transport, the relations between salt hypertension and diet). The teaching of theoretical knowledge is complemented (during the translational course) with patient demonstrations to show the clinical symptoms and to explain how the disease affects the patients’ every day life.

After completion of this course you can:

  • Explain the pathophysiology of inborn errors of energy metabolism and small molecule transport, including the molecular mechanisms.
  • Understand the mechanisms and implications of cell migration and its role in disease.
  • Value the use of bioinformatics, proteomics and structure analysis for diagnosis and molecular understanding of the pathology of diseases.
  • Apply knowledge of the molecular mechanisms of (defects of) energy metabolism and transport of small molecules to define research questions and design research proposals to advance the knowledge in these fields.
Content
This course focuses on MMD Theme 2: Metabolism, Transport and Motion/Metabolic Disorders.It consists of lectures and assignments (21 November-5 December 2016) and a written test (08 December 2016). Together with the subsequent course "Metabolic Disorders" (MED-MM2TR) it forms the Module "Metabolism, Transport and Motion /Metabolic Disorders".
Introduction
Next to the genome and the proteome, the collection of small (in)organic compounds like water molecules, energy and redox metabolites like ATP, NAD(P)H, and ions like Ca2+, Mg2+, K+, Na+, Cl- and others together form a third important network of organization in every cell. Pyridine metabolites like ATP and NAD(P)H are synthesised or utilised in core-pathways of metabolism (glycolysis - OXPHOS) and involved as fuel, electron donors, or co-factors in virtually all relevant interactions between micro- and macromolecular components of the cell. Especially the importance of energy and redox regulation of cell growth, and maintenance of viability and stress response is now well appreciated. Mitochondria are central in this regulation, and abnormal functioning of these organelles and associated pathways is intimately linked to neuromuscular disease, ageing, cancer and metabolic syndrome/diabetes via apoptosis control and metabolic signalling. Similarly, defects in systems for membrane transport of water, drugs and metabolites, regulation of ion levels (channels and ion pump ATPases), or actomyosin-based control of cell dynamics, which directly or indirectly rely on the use of ATP and control the intracellular distribution of ions and small molecular compounds, are cause of disease, including inheritable channelopathies, renal disorders or abnormal sensitivity to pharmacological agents. Motion and more specifically cell migration plays an important role in human health and disease. This process depends on the regulation of the actin cytoskeleton. The main molecular mechanisms driving cell migration and their role in disease processess as cancer invasion and metastasis will be discussed.
In this course we will use examples from international literature and own research to illustrate how the processes of energy and redox metabolism or pump, motor or transport systems are coupled, and what the importance of cellular compartmentalisation is in this coupling in health and disease In particular, the consequences of defects in this integrated network occurring in various inherited and acquired disorders will be discussed. We will also explain how advanced protein mass spectrometry is used to generate proteome data, how 3-D structure data of proteins are obtained. These data can be integrated together with genomic data at the bioinformatic level and used for candidate disease gene and pathway prediction. Studies in this area range from "molecule to bedside" and therefore require multidisciplinary approaches. This core fundamental course emphasizes the development of problem solving and conceptual skills by using conventional lectures, computer-based interactive learning, and small enquiry based theoretical science projects. Students are offered a comprehensive series of introductory lectures on the topics that go beyond basic (Bachelors) knowledge of biochemistry and cell-biology textbooks. Students will be asked to read background literature and use information from websites to make themselves familiar with knowledge on the significance of metabolite profile analysis, (reverse) genomics and proteomics for the study of channelopathies, drug transport, cell dynamics and mitochondrial disorders. Emphasis will be on the value of combined approaches using biochemical, molecular biological, cell biological, physiological and biophysical (microscopy) methodology for clinical diagnosis and therapy. In the last part of the course, students are expected to define a research area of interest, and - based on one or two key papers from literature - conceive a rationale and matrix for a small research project within this area, guided by tutors. A small written report on the research project proposal should be prepared and an oral presentation must be given. After this course students are expected to understand the essence of metabolic and physiological investigations and think and behave as (junior) scientists in the field.
Relation
This is a core course of the Master's programme Molecular Mechanisms of Disease.
Key words
Energy and redox metabolism, mitochondria, cellular migration, regulation of Ca2+ and Mg2+ physiology, water, drug and metabolite transport, bioinformatics of metabolic pathways, metabolic disease.
Examination
The students will be monitored throughout the course. The assessment will be carried out on the basis of the following criteria:
  • Essay Question Exam on aspects of theoretical knowledge acquired from the series of lectures in week 1 (weight 1/2).
  • Product value of the project proposal (includes innovative character, feasibility of planning, clarity of the proposal and other aspects - e.g. participation! -of both the written product and oral presentation combined) (weight 1/2).
Both components must be graded 6.0 or higher to pass the course.
If a student fails the course:
  • In case the project proposal is insufficient, the modified report must be reassessed. If the modified report is still not assessed sufficient, the student must follow the complete course (including project and written test) in the next academic year. In this case, attendance to seminars is not obligatory.
  • In case the assay question examination is graded 5.0 or less, the student must register for and do the resit examination that is scheduled on Wednesday April 26, 2017. Please note that only the grade obtained last counts. If the resit is assessed 5.0 or lower, the student must follow the complete course (including project and written test) in the next academic year. In this case, attendance to seminars is not obligatory.
Literature
  • Assignments and literature are the main materials for this course (See course manual on Blackboard).
  • Core textbook: Lodish: Molecular Cell Biology, 7th edition; in particular chapters 5, 10, 11, 12, 17.
Remarks
Registration for resits to be done in OSIRIS student.
 
Levels
1st year MSc MMD

Instructional modes
Working group
Attendance MandatoryYes

Tests
Written exam
Test weight60
Test typeWritten exam
OpportunitiesBlock 3, Block 3

Research proposal
Test weight25
Test typeProject
OpportunitiesBlock 3, Block 3

Oral presentation
Test weight15
Test typePresentation
OpportunitiesBlock 3, Block 3