Module Specification
The information contained in this module specification was correct at the time of publication but may be subject to change, either during the session because of unforeseen circumstances, or following review of the module at the end of the session. Queries about the module should be directed to the member of staff with responsibility for the module.
Title Biochemical Messengers and Signal Transduction
Code LIFE304
Coordinator Dr PA Eyers
Biochemistry
Patrick.Eyers@liverpool.ac.uk
Year CATS Level Semester CATS Value
Session 2016-17 Level 6 FHEQ Second Semester 15

Pre-requisites before taking this module (other modules and/or general educational/academic requirements):
LIFE202 None 

Modules for which this module is a pre-requisite:
 

Co-requisite modules:
 

Linked Modules:
 

Teaching Schedule
  Lectures Seminars Tutorials Lab Practicals Fieldwork Placement Other TOTAL
Study Hours 23
This refers to timetabled lectures in which core concepts are explained
1
This refers to a timetabled seminar research seminar
        24
Timetable (if known)   Even though only 1 seminar is scheduled, students are encouraged to attend the relevant research seminars.
  		         
Private Study 126
TOTAL HOURS 150

Assessment
EXAM Duration Timing
(Semester)		 % of
final
mark		 Resit/resubmission
opportunity		 Penalty for late
submission		 Notes
Unseen Written Exam  120  Semester 2  80  Yes    Written Examination 
Unseen Written Exam  60 minutes  Semester 2  20  Yes    In-class test Notes (applying to all assessments) The written examination will be an extended piece of writing. The in-class test will be objective tests (such as Extended matching items questions) and/or short answer questions  
CONTINUOUS Duration Timing
(Semester)		 % of
final
mark		 Resit/resubmission
opportunity		 Penalty for late
submission		 Notes
             

Aims

 
To enable students to evaluate and describe the latest knowledge and ideas o n how cells respond to external signals and how signalling information is transferred within and between cells
 
To develop in students an understanding of the range of different strategies used by cells for generating and interpreting signalling information, including their outcomes
 
To introduce students to current knowledge of the molecular and biochemical events that lead from receptor occupancy to changes in gene expression and phenotype, with links to human diseases explained
 
 

Learning Outcomes

To compare, in both written and graphical formats, the multiple molecular processes underlying transduction of information, the key extracellular and intracellular players 

To assess the consequences of expression changes or mutations in signalling proteins in the context of different diseases 

To appraise the features of the major components and modules of signalling pathways

To evaluate the usefulness of signalling proteins as targets for rational drug design

 

Teaching and Learning Strategies

Lecture - This refers to timetabled lectures in which core concepts are explained

Seminar - This refers to a timetabled seminar research seminar

Even though only 1 seminar is scheduled, students are encouraged to attend the relevant research seminars.

Syllabus
1 

         Membranes, Receptors and Ligands
 
- Model organisms/systems used to study cell signalling and the key signalling modules. Properties of membranes relevant for signal transduction and concept of ‘signalling currencies’
-The extracellular matrix
- Extracellular ligands: growth factors and cytokines
-The pathway from membrane to nucleus: cell proliferation in epithelial and immune cells
- Families and classification of receptors: G-protein coupled receptors and drug discovery; ion channel-linked receptors; enzyme-linked receptors: tyrosine kinases. Consequences of receptor activation, inactivation, clustering, desensitisation, turnover
 
Transduction and intracellular signal processing
-Heterotrimeric nature-proteins, 3D structure, role in transduction, isoforms, modification in health and disease, ADP-ribosylation (cholera, whooping cough), acylation and isoprenylation, turnover and regulation
-Cyclic nucleotides: cyclases; phosphodiesterases; isoforms; drug targets and disease. Cyclic nucleotide gated channels: olfaction
-Inositol phospholipid turnover: relative roles of PL-C and PI3 K isoforms; activation mechanisms (e.g. G-protein/ tyrosine phosphorylation); PTEN and SHIP. PI3K delta inhibitors for cancer
-Calcium mobilization. Intracellular calcium homeostasis, pumps and channels,transients and waves. Experimental determination and visualization of calcium mobilization
Role of calcium in intracellular signalling,lmodulin as a calcium sensor,
Calcium-sensitive gene expression (experimental approaches: visualisation) and calcium-sensitive enzymes in signalling
-Signalling by PTMs and their recognition by signalling domains
-Phosphoproteomics and Mass Spectrometry
-Cell cycle concepts and the road to cancer
-Signalling and proliferation, differentiation, polarity, authophagy and apoptosis
 
 
         Protein phosphorylation a nd Ubiquitylation Networks
-The kinome:: comparative phylogeny; model organism kinomes; the human kinome, pseudokinases and diseases/drug development and kinase inhibitors
-Protein kinase A regulation, scaffolding and structure, the kinase domain, metal and ATP binding, mechanism of catalysis
-The phosphatome: Protein phosphatases and mechanism of dephosophorylation, pseudophosphatases: classification; evolutionary aspects (Yersinia). Protei n phosphatases 1 and 2A as ‘master regulators’ of the cell cycle and beyond
- Protein kinase sub-families: AGC kinases; Akt and PKC; isoforms, subcellular distribution; targeting and scaffolding.
Calcium/calmodulin dependent protein kinases,regulation/activation,  calmodulin as a calcium sensor, targets for phosphorylation
-Downstream of PI-3 kinase, PDK1, mTORC1 and mTORC2, GSK3, p70 S6k role in insulin/growth factor/nutrient signa lling and apoptosis
-Receptor Ser/Thr kinases: role in developmental signalling; TGFb; receptor activation; SMADs; accessory proteins; role as tumour suppressors
20,21 The MAP kinase modules of kinase activity, cross-talk, amplification and specificity/targeting of modules and diseases. Transcriptional activation, TRE, SRE
-Protein ubiquitiylati on. E1, E2 and E3, Chain linkage specificity
Ubiquitin is phosphorylated, DUBS, mechanisms,
Proteasomes (link to cell cycle). SUMO/NEDD.
-The protein kinase domain and kinase inhibitors
- Hot topics in cell signalling

Module content will be delivered primarily via interactive lectures, which will be accompanied by suitable lecture hand-outs and linked to a newly published core text which students are expected to use for independent learning. Students will be guided to this text, multiple copies of which have been ordered for the library, and also to specific reviews of source literature, copies of which will be made available online for use by the students. During the module, an opportunity will exist for students to self-evaluate their understanding of the content through an in-lecture quiz. To support independent learning, lectures will be supplemented by a seminar and on-line resources available through VITAL, including a new text written by a central figure in cell signalling, focused review articles and all students will be directed to attend seminars by external and internal speakers in subjects allied to cell signalling, including specific careers advice aimed at students looking at postgraduate research.

Recommended Texts
Reading lists are managed at readinglists.liverpool.ac.uk. Click here to access the reading lists for this module.
Explanation of Reading List:

Hunter T (2012):why Nature chose Phosphate to modify proteins’ Philos Trans R Soc Lond B Biol Sci 367:2513-16

 

Lim, W; Mayer B and Pawson T (2014) Cell Signaling principles and mechanisms (Garland Science)