BSc Thesis Human and Animal Physiology

Human and Animal Physiology is committed to teaching that challenges and inspires BSc students.

Human and Animal Physiology extensive expertise in performing interventions studies focused on assessment of energy metabolism, integrated with metabolic, functional genomic and immune-histochemical analysis. We perform short term interventions and cross-sectional mechanistic studies in humans, detailed short and long term dietary interventions in model animals (mice and pigs), and detailed mechanistic studies in tissues as well as primary and cultured cells.

For BSc students, we offer possibilities to participate in literature studies related to the current physiological research performed at HAP. Research questions focus on the research aims of HAP and thereby contribute to comprehensive mechanistic and physiological interpretation of current scientific findings.

If you are interested in writing your BSc thesis on one of the subjects below, you can contact our secretariat to make an appointment with Dr Sander Grefte to discuss the possibilities.

“Of note: The aim of our chair group is to make a good match between your interests and our BSc thesis topics. This cannot always be guaranteed during period 6 due to the large number of students that sign up. If you are not restricted to period 6 and want to be sure that you can write a BSc thesis on your topic of interest, our advice would be to schedule your BSc thesis during a different time period.”

Click on the title of interest to read more about this topic.

BSc Thesis Subjects

1. Overweight/obesity and female fertility

Background: Overweight and obesity are becoming more and more a serious health problem, not only in humans but also in pet animals. Beside to direct effects on health, obesity in females is also an important cause of fertility problems. In the past few years it has become apparent that the adipokine leptin plays an important role in the initiation of puberty and in adult fertility through its stimulating effects on the kisspeptins. Due to the fact that the kisspeptin neurons are also influenced by sex steroids and project to the GnRH neurons in the hypothalamus, they are thought to play a key role in the regulation of male and female fertility. Aim: To determine why fertility in many overweight/obese subjects is affected, despite the fact that they have elevated leptin levels. - What is the role of the kisspeptin system in overweight/obesity induced fertility problems in females - Why are the effects of overweight/obesity on fertility more severe in females compared to males?

2. Role of the IGF-system in male/female reproduction

Background: The insulin-like growth factors (IGF) have in the past been shown to be important for normal fertility. It is however not clear whether it is the locally (in the gonad) produced IGF is essential for normal fertility or whether systemic IGF (produced by the liver) is also involved, and whether locally produced and systemic IGF make use of the same signal transduction pathway when influencing follicle development in the ovary or Leydig cell/Sertoli cell function and thus germ cell formation in the testis. Aim: To analyse the pathway(s) along which IGF can influence either ovarian follicle development o or the formation of germ cells in the testis, and whether there exist differences in the effects of locally and peripherally produced IGF.

3. Thyroid hormones and fat tissue distribution

Background: When thyroid hormone levels are too low during fetal and postnatal life, metabolism is severely affected. Our experiments have shown that as a consequence of hypothyroidism fat tissue distribution is severely changed, without influencing total body fat content. This immediately raises the question about what the mechanism is behind this change in adipose tissue distribution and the possible consequences for energy metabolism/homeostasis. Aim: To prepare a thorough overview of the present knowledge about the role of thyroid hormone in fat tissue distribution. What is the mechanism behind this change and how does this influence metabolism.

4. Subjects related to the themes in course HAP30806

Integrated Neuroendocrinology Themes: Sleep, emotions, stress, ingestive behaviour, reproductive behaviour, learning and memory, psychopharmacology and drug abuse, neuronal disorders. Aim: To make a literature overview of the physiology of the selected topic. For this thesis subject it is strongly advised that you take or have taken the course HAP30806 (Integrated Neuroendocrinology)

5. Evaluation of infertility in Witrik cattle

Background: Homozygous Witrik cattle are usually infertile. This infertility in Witrik cattle could be due to problems with germ cell migration and/or degeneration of the germ cells after they have reached the testes or ovaries. White spotting variant mice (Wv) have a similar phenotype, so these mice are a good model to study causes of infertility in Witrik cattle. Aim: Perform a literature study to find out the possible cause of infertily in Witrik cattle, including studies of infertile Wv mice.

6. Physical activity and energy metabolism

Background: Physical activity/exercise and energy metabolism are essentially interrelated. Regular physical activity requires adaptations of energy metabolism, and adequate regulation of energy metabolism is crucial for optimal exercise performance. Aim: To provide a literature overview on specific aspects of the interrelationship of physical activity and (cellular) energy metabolism. This could also include effects of nutritional compounds. A more detailed aim is depending on the students’ interest and will be discussed with the supervisor.

7. Hypoxia and energy metabolism

Background: Oxygen is essential for aerobic metabolism of our nutrients, and therefore an important factor in energy metabolism. When subjects are exposed to low oxygen tension (hypoxia), for instance during a stay at high altitude, a loss of body weight is frequently observed. On the other hand, hypoxia is sometimes used to enhance exercise performance, and recent studies suggest that hypoxia may have the potency to treat specific forms of mitochondrial disease. These studies indicate that hypoxia affects energy balance and energy metabolism. Aim: To provide a literature overview on the physiological effects of hypoxia on energy metabolism. A more detailed aim is depending on the students’ interest and will be discussed with the supervisor.

8. Communication between adipose tissue and another organ

Background: Adipocytes secrete a huge number of signalling molecules, the so called adipokines. These can have a function on e.g. muscle, brain, or liver. It is evident that this kind of communication is going back and forth. Questions: What are these adipokines and how do they signal? And what does the alternative organ, e.g. liver, signal to adipocytes? Is this similar in mice and men? Aims: To provide a literature review about one or more questions related to communication to and from adipose tissue (the exact topic will be determined together with the supervisor).

9. Metabolic programming

Background: nutritional interventions in specific windows of opportunity during early life development can have beneficial effects on metabolic health in adulthood. Questions: what is the role of a specific macronutrient (fat, carbohydrate) and can we modulate in this way beneficial health effects by nutrition? Is the effective period during development different for macronutrients? Aims: To provide a literature review about one or more questions related to metabolic programming on a macronutrient of choice (to be determined in consultation with supervisor). Aims: To provide a literature review about one or more questions related to lactate dehydrogenase (the exact topic will be determined together with the supervisor).

10. Should we put cloths on mice for the study of energy metabolism?

Background: Environmental temperatures (Ta) affect thermoregulation in mammalian species including humans. Maintaining the body temperature (Tb) at a relative constant value requires energy. These energy requirements depend on Ta. The energy spend on thermoregulation also affects energy balance and thereby body weight regulation. With the major epidemic proportions of obesity and associated health problems many studies focus on the regulation of body weight, in order to find solutions to the health problems of obesity. Animal models are frequently used, but are mostly performed at standard Ta of around 22 ˚C. Questions: What is the role of Ta on energy metabolism? Is this role the same in humans and in animal models for (disturbed) energy metabolism? Aim: Integrate results from research papers to create a state-of-the art overview answering one or more questions related to this topic (the exact topic will be determined together with the supervisor).

11. The role of inflammation in metabolic complications

Background: Inflammation has been recognized to influence the development of many metabolic complications. Stimuli such as overnutrition, physical inactivity, and aging may result in cytokine hypersecretion and eventually lead to insulin resistance and diabetes. Similarly, a difference in carbohydrate composition, not quantity, in early life can have similar effects. Questions: What is the precise role of inflammation in metabolic complications? Is this role influenced by nutritional status? Is there a general mechanism involved or are specific pathways more predominantly activated? Are inflammatory mediators interesting targets for nutritional and therapeutic intervention strategies? Aims: Integrate results from research papers to create an overview about one or more questions related to this topic (exact topic to be determined in consultation with supervisor).

12. The role of dietary branched chain amino acids in health and disease

Background: A healthy diet likely prevents the development of diseases. Although the composition of a healthy diet is under intense research, particular macronutrients, micronutrients and the balance between different macronutrients seem to be essential. Dietary protein content and its derived amino acids have been proposed to play a role in a number of diseases. Branched chain amino acids (BCAAs) are of particular interest because they are highly elevated in Type II diabetic patients and on a molecular level activate the cellular master-regulator mTOR. Aim: Provide a literature overview of the relation between BCAA intake and disease, as well as elucidate molecular mechanisms how BCAA contribute to disease pathology.

13. Optimizing immune function via the diet

Background: It has been recently discovered that metabolism of immune cells is a critical regulator of inflammatory diseases. This opens up novel opportunities to design nutritional intervention that impact inflammatory diseases. Aim: Provide a literature overview of novel cellular and physiological metabolic processes that impact immune function and design nutritional interventions to strengthen the immune function.

14. Targeting energy metabolism of cancer cells

Background: Cancer cells use glycolysis for energy production, rather than oxidative metabolism which occurs in mitochondria. Mitochondrial metabolism of cancer cells is reprogrammed for biosynthesis rather than energy production. Mitochondria are thus a target for anti-cancer interventions. AMP-kinase is a cellular energy sensor that targets mitochondria and can stimulate oxidative metabolism. AMP-kinase is activated by exercise. Aim: Provide a literature overview of exercise as an anti-cancer therapy. Focus on interventions in model animals and humans, including evidence for the underlying mechanisms that are targeted.

15. Aging, a disease of mitochondrial damage

Background: Mitochondria have a number of essential cellular functions. Mitochondrial quality is constantly monitored and damaged mitochondria, showing reduced membrane potential, are removed by mitophagy. It is postulated that aging is caused by accumulation of defective mitochondria either because of increased damage or because of problems with monitoring mitochondrial quality. Questions: What is the role of mitochondria in the aging process? Which processes regulating mitochondrial functions are affected by aging? Aim: Investigate the evidence for accumulation of damaged mitochondria with aging and describe which markers can be used to assess this in vivo.

16. The molecular link between mitochondrial dysfunction and intestinal permeability

Background: The main function of mitochondria is to produce cellular energy, but they also fulfil other functions such as cellular signalling. It has been shown that energy depletion leads to increased intestinal permeability. This provides a link between mitochondrial (dys)function and intestinal permeability. Questions: Which signalling pathways are affected by mitochondrial dysfunction? Are these pathways involved in maintaining intestinal permeability (i.e. cellular differentiation, tight junctions)? Aim: Integrate results from research papers to create a literature overview that describes the signalling pathways involved in both processes. The aim is to go into depth by describing molecular pathways or the involvement of specific protein(s).

17. The link between redox balance and (mitochondrial) energy metabolism

Background: ATP is generated through cellular respiration in mitochondria, making these cell organelles important for cellular metabolism. Mitochondria are the main source of reactive oxygen species (ROS) as unpaired electrons are generated in the process of oxidative phosphorylation. As a consequence, mitochondria are well equipped with antioxidant defences. High levels of ROS are strongly related to metabolic complications. One protein, the NNT will have a central role in this topic Questions: What is the metabolic consequence of redox balance versus imbalance? What tips the scale? Is this influenced by physiological status like obese or insulin resistant vs healthy? Is this influenced by nutritional status? Is redox state an interesting target for nutritional or therapeutic intervention strategies? Aims: Integrate results from research papers to create an overview about one or more questions related to this topic (exact topic to be determined with supervisor). The aim is to go into depth by describing molecular pathways or the involvement of specific protein(s).

18. Mechanistic role of mitochondria in Alzheimer’s disease

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Brains of AD patients contain amyloid beta (Aβ) plaques and tau tangles. Mitochondria play a large role in neuronal function by constantly providing energy, particularly at synapses. Mitochondrial function is decreased in AD patients. Decreased mitochondrial functioning impacts on synaps function, which could lead to neuronal damage and ultimately to memory loss and cognitive impairment in patients with AD. Ameloid beta, phosphorylated tau and mitochondrial function affect each other, but the sequence of cause and affect are not clear. Relevant questions: What is the evidence that ameloid beta affects various mitochondrial functions and how? What is the evidence that phosphorylated tau affects mitochondrial function and how? What is the evidence that mitochndrial dysfunction can lead to plaque and tangle formation and how? How do ameloid beta and phosphorylated tau affect mitochondrial dynamics and how can this lead to AD? How can dysfunction of mitochondria increase plaque and tangle formation and how can this lead to AD? Ameloid beta, phosphorylated tau and mitochondrial function affect each other, but what is cause and consequence? How is metabolic health (or specific aspects of metabolic health such as insulin resistance) linked to AD? Which mechanisms underlie sex differences in AD susceptibility Aim: Define a specific research question related to one or more of the questions above. Write a logically structured report based on literature research question, focusing on specific proteins/mechanisms involved. Conclude and propose an experiment that brings this research on step further.

19. Effects of statins on mitochondrial energy metabolism

Background: Statins are a class of cholesterol-lowering medication that are very effective in reducing serum cholesterol levels and are known to reduce cardiovascular events with 30%. Myopathy is the most important adverse drug reaction of statin therapy with rates up to 26%. The mechanism underlying the muscle side effects remains enigmatic, but it is suggested that statins disturb mitochondrial energy metabolism via various routes. Relevant questions: What is the evidence that mitochondrial function is disturbed in myopathic statin users? Is the disturbance in mitochondrial function causally related to the muscle complaints patients experience, or is there also evidence that asymptomatic statin users (statins users without muscle complaints) show a diminished mitochondrial function? What are the different mechanisms discussed in literature via which statins disturb mitochondrial function? Aim: Define a specific research question related to one or more of the questions above. Write a logically structured report based on literature research question, focusing mechanisms involved. Conclude and propose an experiment that brings this research on step further.

20. Effects of statins on exercise performance

Background: Cholesterol-lowering statins are prescribed to patients with high cholesterol levels and are known to reduce the cardiovascular events with 30%. Besides statins, physical exercise is advised for dyslipidemic patients. In fact, it is suggested that statin treatment along with a moderate to high physical fitness level provides additional protection against premature cardiovascular death. However, adopting or maintaining a physically active lifestyle is often not feasible for statin users, as 26% experiences muscle toxicity as adverse effect of statins. The practice of physical exercise on top of statin treatment is even thought to blunt the aerobic training response, and exacerbate the muscle complaints. Relevant questions: What is the evidence for a diminished exercise performance and aerobic training response in myopathic statin users? Is there a relationship between exercise performance and muscle complaints in myopathic statin users? What are possible mechanisms that are likely to contribute to the lack of a training response? Aim: Define a specific research question related to one or more of the questions above. Write a logically structured report based on literature research question, focusing mechanisms involved. Conclude and propose an experiment that brings this research on step further.

21. Role of mitochondrial oxidative stress in atrial fibrillation

Background: Atrial fibrillation (AF) is age-related progressive arrhythmia. Mitochondrial dysfunction and oxidative stress are often observed in AF patients. But is mitochondrial oxidative stress or cause for AF in still unclear. Relevant questions: What is the role of mitochondrial oxidative stress in the pathogenesis of AF? What is the potential underlying mechanism? Aim: Provide a literature overview of role of mitochondrial oxidative stress in atrial fibrillation and the involved (potential) molecular signalling pathways.

22. Role of ER (SR) and mitochondrial contacts in cardiac aging and arrhythmia

Background: SR (smooth endoplasmic reticulum (ER) found in cardiomyocytes) and mitochondria, the two central organelles involved in Ca2+ and energy (ATP) homeostasis which are both crucial for normal cardiomyocyte contraction and relaxation. SR stores Ca2+ and plays a major role in cardiac excitation-contraction (EC) coupling in close cooperation with mitochondria, which play a vital role in generating ATP and buffering cytosolic Ca2+. During the EC coupling, Ca2+ is released from SR into the cytosol, allowing Ca2+ to bind to the myofilament troponin-tropomyosin complex, which then initiates myofilament contraction. Proper Ca2+-handling and myofilament contraction and relaxation requires ATP. For efficient ATP regeneration during contraction, mitochondria take up part of the SR-released Ca2+ that stimulates key enzymes of the tricarboxylic acid (TCA) cycle to increase the production of substrates (NADH and FADH2) for the electron transport chain. This close cooperations of SR and mitochondria, termed SR-mitochondrial contacts, are achieved by tether proteins including Mitofusion 2. Changes of SR-mitochondrial contacts may cause cardiac arrhythmia and aging. Relevant questions: How SR-mitochondrial contacts regulate heart function? Aim: Provide a literature overview of role of SR-mitochondrial contacts in the heart with focus on cardiac aging and arrhythmia.