Mitochondrial biology, bioenergetics and metabolism in human disease. Course: CELL 3007

UCL CfMR offers a new undergraduate course:

Mitochondrial biology, bioenergetics and metabolism in human disease.

CELL 3007

To be run by Michael Duchen and Gyorgy Szabadkai

To include a lecture course, practical workshops, and journal clubs.


Faculty website link


Provisional details:

Lecture course: basic principles of mitochondrial cell biology and bioenergetics (90 minute sessions).

1.         Introductory session, MD and GS with biscuits and drinks. Overview of the course general light introduction to mitochondrial biology MD/GS
2.         Energy transformations in mitochondria Peter Rich
3.         mitochondrial ‘quality control pathways’ : i) biogenesis, autophagy GS
4.         mitochondrial ‘quality control pathways’ : ii) trafficking, fission and fusion. Josef Kittler
5.         mtDNA replication, regulation and maintenance; mutations and human disease

 

Ian Holt (NIMR)
6.         Nuclear encoded mitochondrial mutations and human disease (include nuclear transfer issues etc ) Shamima Rahman
7.         Evolutionary biology and mitochondria: Nick Lane
8.         mitochondrial calcium signaling: mechanisms and functional consequences

 

MRD
9.         basic principles of free radical biology – mitochondria as sources and targets of free radicals

 

Amandine Marechal
10.      mitochondrial cell death pathways i) apoptosis GS
11.      mitochondrial cell death pathways ii) necrosis and PTP MRD
READING WEEK
Mitochondria and disease – these will be more seminar style lectures dealing with current research and with PIs presenting more based on their own work.
12.      Mitochondria and cancer 1 cell death pathways and cancer GS
13.      Mitochondria and cancer 2 metabolism pathways and cancer GS
14.      Mitochondria and ischaemia i in the CNS: stroke and excitotocity MRD
15.      Mitochondria and ischaemia ii in the heart: heart attack Sean Davidson
16.      Mitochondria and sepsis M Singer
17.      Diabetes MD and Frances Brodsky
18.      The biology of Ageing David Gems
19.      Mitochondrial dysfunction and Neurodegenerative/neurological disease Helene Plun Favreau
20.      Mitochondrial pathways as therapeutic targets in disease – pathways/pipelines for drug development Workshop with Eisai

Tom Briston

 


Technical workshops: how we study mitochondria: hands on workshops – students will be divided into groups to spend 2h sessions in individual labs. The way these are run will depend on numbers. If we assume 20 students, each workshop will be run for two weeks, and the students will be divided into groups of 5, so that there will be two consecutive sessions on each teaching afternoon.

1.     principles of fluorescence imaging, MD
2.     principles of respirometry MD lab
3.     EPR and measuring ROS Chris kay
4.     Luminescence measurements – aequorin/luciferase GS
5.     mtDNA sequencing Rahman, ICH

 


Mitochondria, metabolism and disease journal clubs: these will be based on student presentations in a journal club style built around reviews and original papers, with two student presentations per week.



Syllabus

The lecture course will cover the major aspects of mitochondrial metabolism and mitochondrial biology. This will start with explorations of basic principles of energy conversions, the respiratory chain and electron transfer, mitochondrial structure and function and the mechanism of ATP synthesis. This will then move on to mitochondrial quality control pathways, including autophagy and biogenesis pathways and their modulation, trafficking, fission and fusion. The lectures will consider basic biological mechanisms but also explore the roles of these pathways in health and in disease. The next major topic will be the behaviour of mitochondrial DNA, how this is conserved, its replication, transcription and translation, its packaging in nucleoids, the consequences of mutations and issues related to mitochondrial heteroplasmy and the regulation of copy number. We will consider the diseases associated with mutations of mtDNA and consider potential therapeutic strategies, moving on to explore the newly emerging mutations of nuclear encoded mitochondrial proteins and their roles in human disease. We will then consider pathways of mitochondrial interaction with the cell, especially in relation to calcium signalling and free radical signalling. Calcium signalling will be explored especially in terms of the modulation of oxidative phosphorylation by calcium in relation to cellular activity, but also in terms of its impact on cell signalling through local calcium buffering. Mitochondria are also major targets and generators of free radical species – this is a field which is often muddled and inaccurate and it will be important to ensure that students understand what free radicals are, how they are generated and how they behave. For this we will bring in a guest lecturer who is expert and will talk about these issues as well as models of free radical generation and their roles in disease and modulation of free radical generation by uncoupling proteins. Mitochondria are the gatekeepers of cell death pathways that are critically important in cancer and in ischaemic injury and other diseases. Two lectures will then focus on pathways to cell death and their modulation in disease and by pharmaceutical approaches.

These lectures provide a core introduction to principles of mitochondrial biology and metabolism. In the latter part of the course, the lectures will become more informal seminar style talks in which lecturers will be asked to provide more research type data, with some focus on their own work. These will deal primarily with the roles of mitochondrial and metabolic dysfunction in specific diseases, including cardiovascular disease, stroke and myocardial infarction, cancer, neurodegenerative and neuroinflammatory disease, sepsis and ageing.

One ‘guest’ lecture will place mitochondria in evolutionary time and will explore the evolution of the modern animal mitochondria – how did they originate, why might the mitochondrion retain a genome, why haven’t all genes been passed to the nucleus etc.

A further ‘guest’ lecture from a colleague in Industry will look at drug development pipelines and explore what is involved in target identification and validation, drug development and drug discovery and how these can lead to therapeutics that reach the market place.

The lecture series will be supported by laboratory based ‘technical workshops’, which will focus on operational issues of techniques used to study mitochondria and will be presented to the students as essential to understand their reading. We will ensure ‘engagement’ as one component of the exam will require an understanding of the technical elements. The objective is to provide students with an understanding of the technical issues that underpin the biology and result in students who will be well placed to apply for Masters or PhD programmes in the field.

 


Examination: 80% of the mark will come from an examination.

20% from a presentation, Based on journal club and a talk

 


Provisional timetabling: term 2

Lecture Monday 2-4 and Friday morning, 11-1; lab visits and journal clubs Friday afternoon. JC 2-3 lab visits after.

 

Exam structure:

Part A several compulsory short answer questions to test breadth of basic knowledge and to include methodological questions   for 2/3 of the mark

Part B an essay focused on one aspect that can be either basic science or more clinically relevant

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