Basic Lectures

Physiology as Science

Physiology (from Ancient Greek: physis meaning nature/origin and logia meaning knowledge of) is an ancient discipline in biology dating back to at least 420 BCE. Physiology focuses on how organisms, organ systems, organs, cells and biomolecules carry out the normal functions in a living system. In this course we focus on mammalian (including human) physiology. The scientific study of physiology has been ongoing since the time of the ancient Greeks until present and now includes many modern methods such as qPCR, immunoblotting, genetic modification of animals and cell cultures.

Nerve Physiology

Nerves connect animal organs together and process information. Nerves function by creating an electrical gradient by pumping ions in and out of themselves. The electrical gradient is transmitted along the long axons of nerves by the action of voltage-gated channels. At the end of these axons lies the axon terminal. Here the electrical signal causes release of specific chemicals, called neurotransmitters, which can inhibit or stimulate the receiving nerve or organ.

Muscle Contraction

Muscles are central to animal mobility, blood circulation and digestion. There are three main muscle types: skeletal, cardiac and smooth muscles. When the brain signals the skeletal muscles to contract, actin and myosin filaments to go into a cycle where they bind and pull on each other. This action causes the myosin and actin filaments to slide over each other, contracting the muscle and extracting force.  

Respiration

Respiration extracts oxygen from the air, as well as deposits gaseous waste products. The lungs accomplish respiration by transferring oxygen from the air breathed in to the blood. Inside the lung there are many airways leading to small pockets (alveoli) surrounded by blood vessels. The alveoli have very thin membranes, which allow oxygen to diffuse over to the blood.

Circulation

Circulation of blood in animals is central to the transport nutrients, depositing of waste products and communication. The circulation of blood is accomplished by the hearth, which is constantly beating throughout life. The blood circles around the body in a system of arteries, veins and capillaries to nearly every cell in the body.

Excretion

Excretion is the disposal of waste products from a living system. In this lecture we focus on liquid waste products expelled by urine. Urine is produced by the kidneys, which filter blood in the Bowman’s capsule, return useful substances and concentrate the urine by extracting excess water. The kidneys also maintain salt balance and blood pH by maintaining a balanced excretion.

Physiology of the Senses

Senses are information-gathering systems which animals use to gain information about their surroundings. Humans have five primary senses: sight, smell, taste, hearing and touch. Sight comes from photons interacting with receptors. Smell and taste comes from molecules binding to specific receptors. Hearing and touch comes from mechanoreceptors detecting motion.

Temperature

Endothermic (warm blooded) animals are distinguished from ectothermic (cold blooded) animals by their ability to uphold a stable body temperature. A stable body temperature is upheld by a variety of methods. It is increased by general metabolism, shivering and brown adipose tissue. It is decreased by evaporation (sweating, panting). Altering insulation (blood flow, piloerection) can both increase and decrease body temperature.

Endocrinology

The endocrine system consists of several endocrine glands secreting hormones into the circulatory system. These serves as a communication system slower, but longer acting, than the nervous system. The endocrine system has many important functions, including regulating homeostasis, metabolism, proliferation and differentiation of cells and for establishing secondary sex characteristics.

Nutrition

Food consists of nutrients. Macronutrients consist of carbohydrates, fat and protein and micronutrients consist of minerals and vitamins. Nutrients are required to give animals chemical energy as well as chemical building blocks. The digestive system is a collection of several organs, which digest and absorb nutrients. What we should or should not eat is a hotly debated topic with few clear answers.

Advanced Lectures

Glucose Uptake

Glucose is taken up by cells and is used as an energy source. There are several glucose transporters (GLUTs) with varying regulation, capacity and affinity. Insulin positively regulates some of these transporters, for example to increase glucose uptake in muscle and fat after a meal. Chronically high levels of blood glucose and therefore insulin lead to insulin resistance and type 2 diabetes.

The Sympathetic Nervous System

The sympathetic nervous system is, along with the parasympathetic nervous system, part of the autonomic (unconscious) nervous system. The primary process of the sympathetic nervous system is to activate the “fight or flight” response. It increases heart rate, blood flow to muscles, increases airflow in the lung and constricts blood flow to the digestory system.

The Physiology of Brown Fat

Brown fat is a heat-producing organ. It functions by uncoupling the proton gradient created by the respiratory chain by the function of UCP1. This gives rise to a “futile” cycle where protons are pumped in and out, releasing heat. Brown fat is recruited by cold exposure and is under the control of the sympathetic nervous system.

Fat-synthesis and Function

Fat has many functions. It is the primary energy deposit in animals and can store the energy required for metabolism for several months in humans. Fat is also a building block of membranes, which keep cells and compartments in them physically separated. Fat is synthesised up to 16 carbons in length by fatty acid synthase. For longer fat chains the action of different ELOVLs is required.  

Intracellular Signaling: cAMP and Metabolism

Cyclic AMP (cAMP) is produced by adenylate cyclase from ATP and is an important secondary messenger in many signalling systems. cAMP is part of the regulation of metabolism in several ways. It is part of proliferation signals in both white and brown fat. cAMP also promotes gluconeogenesis in liver and promotes β-cell expansion and insulin secretion in pancreas.

cAMP and Gene Expression

G-protein coupled receptors (GPCRs), is an important receptor family for several signalling pathways which effects gene expression. Activation of GPCRs can, among other targets, lead to activation or inhibition of AC. AC causes accumulation of cAMP in the cytosol, which activates PKA. PKA in turn have many downstream targets, including the transcription factor CREB. CREB enhances the transcription of several genes.

α-Adrenergic Receptor and Intracellular Signals

There are two α-adrenergic receptors; α1 and α2. α1 is coupled to a Gq GPCR causing activation of PLC. PLC cleaves PIP2 into IP3 and DAG. These activate PKC, which phosphorylates many downstream targets depending on isoform and tissue. IP3 also causes the release of Ca²⁺, which also activates several downstream targets such as calmodulin.

Regulation of UCP1 Gene Expression

UCP1 is an uncoupling protein found in brown fat, central to its function. The gene expression of UCP1 is induced by noradrenaline, PPARg agonists, all trans-retinoic acid and thyroid hormones. Noradrenalin increases UCP1 expression by acting upon β3 receptors; a GPCR which leads to CREB phosphorylation. CREB binds to CRE on the UCP1 gene’s promoter region, causing enhanced transcription.

Receptor Tyrosine Kinase, JAK/STAT

Receptor tyrosine kinase is a signalling pathway responsible for conducting signals from growth factors, cytokines and hormones such as insulin. The JAK/STAT signalling pathway is a subset of a receptor tyrosine kinase. When a ligand (usually a cytokine) binds JAK phosphorylate the receptor, allowing it to bind STAT. STAT is then phosphorylated by JAK, allowing it to enter the nucleus and activate several gene transcription targets. 

Mitochondria: Bioenergetics and Uncoupling Proteins

Production of ATP (chemical energy) occurs in three steps from glucose: glycolysis, the Krebs cycle and oxidative phosphorylation in the electron transport chain. In the electron transport chain protons are pumped out into the intermembrane space and is then released through ATPsynthase. Uncoupling protein 1 (UCP1) releases the proton gradient without creating ATP, leading to heat production.

Reactive Oxygen Species and Antioxidant Systems

Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen, such as superoxide, peroxidase and hydroxyl radicals. Production of ROS has been linked with aging, cancer and many other health effects. Many biological processes create ROS, including mitochondrial respiration. The production and elimination of ROS is tightly controlled.

Hibernation, Obesity and Fever

Hibernation is an energy preservation state utilized by many mammals in winter when temperatures are cold and food is scarce. Brown fat is an important mediator for arousal from a state of hibernation as muscle shivering does not function at cold body temperatures. Brown fat is also a facultative mediator of fever to raise body temperature and a lack of brown fat has been linked to obesity.

Applied Lectures

Research and Education

Research and education is a complex world with various regulations that differ between countries. In this lecture the world of a scientist is explained with respect to what doctoral studies and postdoctoral studies entail, as well as further scientific career with focus on the Swedish education system. Additionally the process of publishing data in peer-reviewed journals is discussed.

Indirect Calorimetry

Calorimetry is measuring the heat production from a reaction, for example an animal’s metabolism. In indirect calorimetry the metabolic rate is measured by proxy, from the consumption of oxygen and the production of carbon dioxide. Measurements by indirect calorimetry not only give the animal’s metabolism but also the respiratory quota, indicating what kind of nutrient the animal consumed.

Manipulating the Genome

Genetic modification of mice is a relatively recently developed method for studying the effect of a specific gene on a parameter of interest. Mice are the most common mammal to be genetically modified due to well-developed methods, a sequenced genome, rapid breeding time and low cost of housing. Recently methods for conditional and tissue specific genetic alteration have been developed.

Binding, Michaelis-Menten

The binding of a ligand to a receptor is of paramount importance to all signalling pathways. The kinetics of an interaction is of interest to develop drugs interacting with a receptor and can be studied in various ways. Michaelis-Manten is the most used model for binding. It relates the binding rate or enzyme activity to the concentration of a ligand or substrate used. 

Animals in Research

Animals have long been used as model organisms in biomedical research. Research on animals has been instrumental to develop cures and preventions for many diseases, including developing vaccines and antibiotics. The most common mammalian model organism is the mouse, followed by rats, due to their small size, rapid breeding time and well-developed methods.

Elementary Statistics

Statistics is central to all science. It is a mathematical model to determine how likely it is that a result acquired is merely due to chance. Scientific data in biology is usually presented with bars displaying the standard error of the mean, showing how much the samples varied in relation to their mean. Also stars are included, showing the probability that the detected result was not due to chance.

Scientific Presentation and Publication

Communicating your results, protocols and experiences is instrumental to all science. An oral presentation should have a clear structure, be repetitive on important points and arouse interest in the audience. A written publication is a formal way of presenting results and ideas. They usually have a set structure of an abstract, introduction, materials and methods, results and discussion depending on the journal. They are usually peer-reviewed, read and commented on by other experts in the field.