Gene and Cell Processes and H1 Key Molecules in Haematology 2023 PDF

Key Molecules and Processes in Haematology Lisa Crawford September 2023  Learning Outcomes 1. To recognise the diversity of biomolecules such as DNA, RNA and proteins 2. To become aware of haematopoiesis as a process 3. To become familiar with some o...

Key Molecules and Processes in Haematology Lisa Crawford September 2023  Learning Outcomes 1. To recognise the diversity of biomolecules such as DNA, RNA and proteins 2. To become aware of haematopoiesis as a process 3. To become familiar with some of the cytokines and hormones involved in blood cell production 4. To appreciate the role of erythropoietin 5. To understand the relationship between structure and function of myoglobin and haemoglobin Key Molecules in Haematology Part 1: A Refresher  The Cell All living organisms are made up of cells Similarities between all Differences, e.g., cell wall in plants Basic unit of life Cells contain organelles, proteins, etc -some seen in all cells, some specialised for function (1) nucleolus (7) Cytoskeleton (2) nucleus (8) smooth endoplasmic reticulum (3) ribosomes (little dots) (9) mitochondria (4) vesicle (10) vacuole (5) rough endoplasmic reticulum (ER) (11) cytoplasm (6) Golgi apparatus (12) lysosome (13) centrioles within centrosome  G = gap G0 Figure 17-4 Molecular Biology of the Cell (© Garland Science 2008) Relationship of DNA to Chromosomes telomere centromere p q  How does this replication work? 06_02_DNA Preferential nucleotide template.jpg pairing (A/T & G/C) means that each strand acts as a template for forming its complementary strand So – DNA acts as a template for its own duplication. Template and new 06_03_own (daughter) strands duplication.jpg are chemically identical.  KEY CONCEPTS (1) the DNA double helix is a spiral ladder-like structure its backbone is comprised of alternating deoxyribose and phosphate groups and its rungs formed by complementary pairs of A-T and G-C bases The DNA double helix is antiparallel DNA winds tightly around histone proteins to form nucleosomes which in turn wind into an even tighter structure to form chromatin DNA replication is semi-conservative 07_01_Genetic info.jpg  THE PROCESS OF TRANSCRIPTION 3 stages – initiation, elongation & termination Many identical copies are simultaneously transcribed THERE ARE 3 MAJOR TYPES OF RNA Messenger RNA (mRNA) carries the information that specifies a particular protein product Each 3 mRNA bases in a row form a genetic code word (codon) that specifies a certain amino acid Specialised cells carry out particular functions because they ‘express’ certain mRNAs (transcripts) Ribosomal RNA (rRNA) – associates with certain proteins to form a ribosome providing a structural support for protein synthesis Made up of a large and small sub unit that are separate in the cytoplasm but join at the start of protein synthesis Transfer RNA (tRNA) – adaptor molecule to match amino acids to codons in mRNA Terminates with CCA where a particular amino acid binds Anti-codon binds complementary mRNA codon Loops represent areas which interact with the ribosome 07_21_nucl_sequence.jpg Membrane associated proteins have many key roles  08_03_control.steps.jpg Remember……..levels matter! Key Molecules in Haematology Part 2 Fat cells Bone  Haematopoiesis Bone marrow 2.3 million new red cells every second 138 million every minute 2 x 1011 per day! Peripheral blood 1.45 x 1015 in 20 years!  Schematic representations of haematopoiesis (A) Classic model in which the haematopoietic stem cell makes an irrevocable choice between the myeloid and lymphoid pathways. (B) The pair-wise model. Differentiation options are envisaged as a series of invariant pair-wise developmental relationships with cells becoming gradually biased towards producing one cell type or another. Brown & Sanchez-Garcia, Oncotarget 2015;6:41 Alternative routes to neutrophils and monocytes. Colony forming cell assays for human hematopoietic progenitor cells Key Molecules in Haematology Part 3 Red Blood Cells (a) as seen on blood film (b) stylised to explain structure & function Red Blood Cell Maturation What is EPO? - haematopoiesis -  What is EPO? - recombinant human EPO - The cloning and expression of human erythropoietin (EPO) was first described by Lin et al. in 1985. ⚫ Recombinant erythopoietin (r-hEPO) is used to treat patients with EPO- dependent nonregenerative anaemia. What is EPO? - An alternative therapy? - OXYGEN TRANSPORT  A tale of two proteins Haemoglobin Myoglobin Iron-containing oxygen transport protein in Primary oxygen carrying pigment of red blood cells of all vertebrates muscle Carries oxygen from the respiratory organs Diving mammals such as whales and seals to the rest of the body have muscles with particularly high There is releases oxygen to permit abundance of myoglobin aerobic respiration for metabolism Haemoglobin chains (crypt notes)  Summary Haematopoiesis is the process through which mature blood cells are produced from a common haematopoietic stem cell Specific growth factors regulate the growth, survival and differentiation of haematopoietic progenitor cells Erythropoietin (EPO) is essential for red blood cell production The structure of haemoglobin is essential for its function in oxygen transport