Detail of Projects

Developmental Biology

Conservation of the germ cell development program in mammals

Dr R Alberio

Primordial germ cells are the precursors of the mature gametes, the cells required for mammalian reproduction. Across metazoans the signalling pathways employed for specifying the germline differs substantially between animals. In mammals, germ cell specification occurs at the epiblast stage, just before gastrulation begins. A few cells in the embryo activate the expression of the transcriptional repressor Blimp-1 (Prdm1). These cells, which are relocated to the base of the allantois, will initiate the germ cell specification program when they activate the expression of the germ cell gene Stella. The initiation of the germ cell program involves a complex gene expression dynamic and epigenetic reprogramming of the genome that leads to the acquisition of totipotency in female gametes. We are investigating this natural reprogramming system to elucidate the sequence of events leading to the acquisition of totipotency. We use a combination of gene expression profiling and analysis of epigenetic modifications in the chromatin of cells undergoing developmental reprogramming for understanding the fundamental mechanisms of cellular de-differentiation. Our experimental system uses the pig embryo as an alternative to the mouse model for mammalian development, which has been used conventionally for establishing principles of development. The pig embryo, in contrast, is an excellent model for establishing principles of development in embryos sharing similar embryonic dynamics (such as human), and to establish the conservation in developmental mechanisms across mammals.

Lineage segregation during embryo development in mammals

Dr R Alberio

The early decisions of the mammalian embryo involve first the segregation of the embryonic and extraembryonic cells that contribute to the formation of the foetus and the placenta, respectively. This is followed by the cells in the embryonic compartment (i.e inner cell mass or ICM) undergoing a second lineage segregation resulting in the formation of the epiblast (primitive ectoderm) and the hypoblast (or primitive endoderm). The cells of the epiblast contribute to all cells in the foetus, whereas the cells of the hypoblast contribute to the formation of the yolk sac and the definitive endoderm. The ICM cells of the mouse can be isolated and propagated in vitro in the form of embryonic stem cells. These cells have the potential to differentiate to all somatic cell types, however, they fail to give rise to trophoblast efficiently. Human embryonic stem cells are also derived after plating human blastocysts, however it is well established that these cells in vitro maintain characteristics of epiblast like-cells rather than ICM-like cells. The difference in the ability of different cellular states in sustaining the propagation of human and mouse ESC in vitro highlights developmental differences between human and mouse embryos. In farm animals, the derivation of embryonic stem cells has proven difficult, and part of the difficulty is due to the limited knowledge of the molecular embryology of farm animal embryos. The development of novel sequencing technologies and the availability of the genome sequences for many farm animal species allows us to investigate the mechanisms involved in the establishment of pluripotency in domestic animal embryos. We are using this knowledge to establish the developmental pathways employed by these mammalian embryos and to develop new strategies for the generation of pluripotent cell lines in farm animals.

Development of the limb muscles

Dr D Sweetman

During development trunk muscle cells are produced in somites where they express the transcription factor Pax3. As these cells differentiate they begin to express markers like Myf5 and MyoD and downregulate Pax3. However the muscle cells which will contribute to the limb musculature maintain Pax3 expression and migrate into the limb bud under the control of HGF signals. Only later, after they have formed two blocks (the dorsal and ventral muscle masses), do they begin to differentiate. The signals driving differentiation in somites are known (Wnt and Shh) but it appears that the process in limb muscles uses distinct mechanisms to induce differentiation. We are examining these signals to improve our understanding of the mechanisms used to generate the limb musculature.

MicroRNAs in muscle development

Dr D Sweetman

MicroRNAs are small, non-coding RNAs which regulate the expression of a wide range of genes. During muscle cell differentiation several microRNAs are expressed including the so called myo-miRs, miR-1, miR-206 and miR-133. These are known to play important roles in muscle differentiation and previous work has implicated them in somite myogenesis during development. Several lines of evidence suggest that although they are expressed in limb muscles their role may be distinct from that in somites. To examine this we use the chicken embryo as an amenable model system to determine the functions of myomiRs in limb development. I am also interested in characterising other muscle specific microRNAs which may regulate myogenesis during development.

Chromosomal modification during development

Improving Development of Somatic cell Nuclear Transfer Embryos

Prof K Campbell

Following fertilisation, development of the early embryo and subsequent conceptus involves cellular growth and differentiation to produce all of the cell types which subsequently result in functional offspring. Following fertilisation the one cell zygote is said to be totipotent, as it can result in differentiation to all cell types. As development proceeds, totipotency is lost and individual cells become progressively more specialised or differentiated. However at specific points in development and also in specific tissues populations of cells have been identified which are able to differentiate to progressively fewer cell types. The mechanisms which control early development and differentiation are complex involving spatial and temporal changes in the patterns of gene expression which are regulated by interactions between cell types and the growth environment. Alterations in chromatin structure have been shown to alter gene expression profiles and also to be heritable during cell division demonstrating that DNA sequence is not the primary determinant. The study of such changes in chromatin structure, termed 'epigenetics' has provided evidence that alteration of the 'epigenome' is involved in a range of processes including predisposition to physiological disorders and development of disease states such as cancer. Thus altering the epigenetic status of a cell can alter its differentiated or functional state. The production of 'Dolly' by somatic cell nuclear transfer (SCNT) the sheep demonstrated that the nucleus from a differentiated cell could in fact be 'reprogrammed' by oocyte cytoplasm and result in the production of live offspring. Using in-vitro and in-vivo oocyte maturation systems in domestic animals and rodents we are studying epigenetic regulation during early development of fertilised and SCNT produced embryos in order to define the mechanisms of nuclear reprogramming which are occurring. Studies involve techniques in gene expression, proteomics, DNA sequence analysis to determine methylation changes, immunofluorescence and chromatin imaging.

Epigenetics, Development and Differentiation

Prof K Campbell

Although now successful in a range of species including sheep, cattle, mice, goats, horses, cats, dogs, rabbits and rats, SCNT is inefficient with losses occurring at all stages of development and also losses in the live born offspring. By studying epigenetic mechanisms as described above we are trying to develop methods to increase the success of SCNT. Studies involve choice of donor cell types, methods for cell and embryo culture, comparisons of cell cycle stages of both donor and recipient cells, alterations in oocyte maturation protocols and methods to alter the epigenetic state of the donor cell prior to SCNT.  These studies are carried out in both domestic species and laboratory based rodents.

Genetically altered Animals for Agriculture and Research

Prof K Campbell

Somatic cell nuclear transfer (SCNT) provides a route for the precise genetic modification of species where embryonic stem cells are not available. Genetically altered animals have a wide range of uses in agriculture and research. Historically, the mouse has been used extensively to study gene function however, other species may provide more suitable models to study physiology and the disease state. To this end we are developing strategies to improve gene targeting in primary cell lines, improve SCNT in cattle, sheep and pigs and develop SCNT in the rat.

Mitochondrial Inheritance and Function in Nuclear Transfer Embryos

Prof K Campbell in collaboration with J. St John, Univ of Birmingham)

MtDNA is a key component of metabolic function in all mammalian species. It contributes 13 of the 70+ subunits of the electron transfer chain (ETC) complexes, associated with the process of oxidative phosphorylation (OXPHOS). The ETC is unlike any other cellular apparatus as it relies on gene products being derived from both the mitochondrial and nuclear genomes and  expression of both nuclear and mtDNA genes is vital for cellular function, as demonstrated by mutation or deletion which can result in severe cellular impairment. Mitochondria are primarily inherited maternally in the oocyte cytoplasm resulting in an individual having only a single mitochondrial genotype. Nuclear transfer bypasses this natural mechanism and results in the transfer of donor somatic mtDNA to the embryo resulting in heteroplasmy. We have shown that nuclear derived transcription factors preferentially activate the donor mtDNA which may lead to mtDNA imbalance. If somatic mtDNA is removed from the donor cell prior to nuclear transfer then homoplasmy is achieved. We have produced live lambs by SCNT from depleted cells and are presently examining the possibility of altering oocyte mtDNA to allow trans-species SCNT. This would be of benefit for conservation in species where female numbers are low or for the production of autologous hES cells.

Ex-Ovo Reprogramming of Somatic Cells

Prof K Campbell , Dr R Alberio

As demonstrated by the success of nuclear transfer experiments, the mammalian oocyte is able to reprogram gene expression of nuclei from differentiated cells to recapitulate development and produce live offspring. Although an inefficient process it is interesting that in the mouse the frequency of isolation of embryonic stem (ES) cells is similar from fertilised or cloned embryos. In human medicine hES cells provide a route to the development of therapies for numerous diseases involving loss or damage of cells and tissues or to gene therapy. However, as with any transplant, immunocompatability of donor cells with the host must be achieved. Two approaches to this problem have been suggested, firstly the establishment of cell banks which would cover the major HLA haplotypes or secondly the production of autologous embryonic stem cells by therapeutic cloning. Autologous ES cells would be preferable, however, due to restrictions in the availability of human oocytes coupled with legal moral and ethical constraints it would be preferable to develop alternative strategies. Amphibian oocytes and eggs are large and easily obtained. Using cytoplasmic extracts prepared from these we have demonstrated aspects of epigenetic reprogramming of mammalian somatic nuclei. DNA demethylation is involved in reprogramming and can be achieved by this system. Using a proteomics approach we are currently identifying amphibian factors which can modify the mammalian epigenome.

Stem Cells in Domestic Animals

Prof K Campbell

Embryonic Stem (ES) Cells have isolated from a range of early embryo stages including morula and blastocysts in mouse, human and mokeys. However, to date there are no reports of proven ES cells in domestic animal species. Interest in human ES cells involves their potential use for cell transplantation for novel human therapies as well as vectors for gene therapy. In domestic species ES cells would have a number of uses firstly they may prove ideal donor cells for animal cloning studies or highly efficient at homologous recombination (as in murine ES cells) for the production of genetically altered offspring for research, to modify production traits or induce disease resistance for agriculture. In addition as is suggested for human cell therapies domestic animal ES cells could be used  for veterinary therapies in companion and or competiton animals. We are currently working on the isolation and characteristion of ES like populations in cattle, sheep and pigs. Information gained from these studies will be used in the future to isolate ES cells from canine and equine species.

Fetal programming during development as a cause of adult disease

Role of nutrition in expression of genes associated with disease, and influence of maternal diet on the subsequent disease development

Dr K Sinclair

Current research is addressing the hypothesis that maternal nutritional effects in developing oocytes and procedures used in assisted reproduction canprogram fetal development and adult health via heritable epigenetic changes inDNA methylation at specific gene loci in the oocyte and pre-implantation embryo. Work supported by the National Institutes of Health (USA) is currently assessing the effects of diets deficient in specific amino acids (e.g.methionine) and members of the B group of vitamins (e.g. folic acid and vitamin B12) on epigenetic modifications to DNA methylation, and pre- and post-natal development in both the sheep and rat, with specific reference to cardiovascular function and the onset of type II diabetes. These studies are being conducted incollaboration with reearchers at the Rowett Research Institute in Aberdeen, and elsewhere at the University of Nottingham; and are complemented by a BBSRC funded program of work that utilises several human embryonic stem cell lines to assess theeffects of perturbed methyl cycle activity on DNA methylation and geneexpression in undifferentiated cells and cells that have been differentiatedinto cardiomyocytes. Additional studies in sheep and human granulosa cell lines, are investigating the effects of omega-3 and -6 fatty acids on somatic and germ cell development and gene expression makinguse of an ovine specific cDNA macroarray.

Reproduction and Fertility

Ovarian biophysics and oocyte maturation

Dr M Luck

Ovarian follicles are cooler than you might expect. Despite being embedded in the abdomen, follicles may be up to 2°C cooler than surrounding tissues, including the rest of the ovary. This curious phenomenon requires explanation: what mechanism allows it to be so, and what advantage does it give to the developing oocyte? A possible mechanism would be endothermic (heat-absorbing) reactions taking place in the follicle. Using a sensitive microcalorimeter, we found that follicular fluid absorbs heat energy when hydrated. We hypothesise that the hydration of internally secreted macromolecules, by water obtained from the circulation, keeps the follicle cool as it grows. Our mathematical models show that these reactions would be sufficient to keep a follicle cool, provided it continues to grow as normal towards ovulation. We are currently investigating the hydratable molecules and their cellular source.

What would be the advantage of a cool follicle? Our experiments with pig oocytes show that the speed of nuclear maturation is slower at lower temperatures. The system is sensitive: maturation takes 12-24h longer for each degree of temperature between 39°C (pig body temperature) and 35.5?C (the coolest follicle temperature). Oocytes are less fertile at low temperatures but can be protected from disadvantage using FSH and follicular fluid, and it may be that slower development gives better embryos. Interestingly, oocytes are temperature sensitive only during early meiosis: changing temperature after the germinal vesicle stage has no effect, even though meiosis-regulating kinases show delayed activation and subsequent maturation is slower. We don't yet know why this is, but heat shock proteins appear to be involved. This research will help us to understand the complex physiology of the ovary, follicle and oocyte and may also help to improved in vitro techniques in assisted reproduction and fertility research.

Follicle oocyte development and interactions

Prof M Hunter

Communication between the oocyte and follicular somatic cells is vital for follicle development and it is becoming clear that the oocyte plays an active role in determining the fate of the somatic cells. We have shown that the porcine oocyte secretes a factor which alters steroidogenesis and proliferation by granulosa cells in culture and that there is paracrine interaction between the different somatic cell types, the granulosa and theca. Furthermore, follicular secretions themselves influence the 'quality' of the oocyte and hence embryo development and survival. Our research aims to elucidate these interactions, using a variety of approaches both in vivo and in vitro. For example, we are using state-of-the art proteomics to identify novel oocyte secreted proteins that regulate somatic cell function. We are also using nutritional manipulation of pigs to alter the pattern of follicle development, the intra-follicular environment and hence oocyte quality and ultimately embryo survival.

Physiological regulation of ovarian angiogenesis

Prof M Hunter , Dr GE Mann and Dr R Robinson, Vet School

A delayed rise in post-ovulatory progesterone is associated with poor embryo development in the cow and it is well established that angiogenesis/vascular development is critical for luteal function and progesterone production. The growth and development of the corpus luteum (CL) is extremely rapid and is dependent on intense physiological angiogenesis. The rates of tissue growth and angiogenesis are phenomenal, equaled only by the fastest growing tumors. Furthermore, the CL has one of the greatest rates of blood flow per unit of tissue and ovarian blood flow is highly correlated with the rate of progesterone secretion.

The overall aim of our research is to understand the physiological regulation of angiogenesis during the follicular-luteal transition and subsequent luteal development. We have investigated the expression and localisation of key angiogenic factors (e.g. VEGF, FGF) in CL recovered from cows at specific stages the cycle and found that FGF, which has often been overlooked,  is more dynamic than VEGF during the follicle-luteal transition indicating a major role at this time.  We have also developed a novel luteal-endothelial co-culture system culture system in which endothelial tubule-like structures develop in vitro from enzymatically dispersed cells (including small, large luteal, endothelial and fibroblast cells) from the bovine corpus luteum.  After 9 days in culture, the tubule-like structures lengthen, thicken and form highly organised intricate networks, which superficially resemble a capillary bed. This culture system provides the ideal link between whole animal physiology and molecular/cellular studies and we will use it to test several hypotheses regarding the regulation of ovarian angiogenesis.

Maternal recognition of pregnancy

Prof APF Flint

Following fertilisation, the early blastocyst enters the uterus where it communicates it presence to its mother. This process (The Maternal Recognition of Pregnancy) ensures the maintenance of the corpus luteum, which by secreting progesterone stimulates the production, by the uterus, of materials required for blastocyst growth and development. The signal produced by the blastocyst at the maternal recognition of pregnancy differes in different species; in man and other primates it takes the form of a chorionic gonadotrophin, while in ruminants it is an interferon.

Blastocyst interferons act by preventing the expression of the oxytocin receptor in the uterus. If the oxytocin receptor is expressed, it interacts with oxytocin secreted by the corpus luteum, to induce episodes of secretion of prostaglandin F2alpha, which cause regression of the corpus luteum (luteolysis). By blocking oxytocin receptor expression, the blastocyst prevents luteolysis, and ensures luteal maintenance.

The tissue in the uterus involved in these processes is the endometrium. The endometrium consts of two principal cell types, an epithelium lining the uterine lumen, and and underlying stroma. When the oxytocin receptor is expressed, in the absence of a blastocyst, it is expressed in the epithelium. A by-product of oxytocin acting on its receptor is arachidonic acid, which travels to the stroma, to act as a paracrine messenger. We are interested in how arachidonic acid acts at the stroma, and also whether its actions can be modified by nutritional influences, for instance through diets high in polyunsaturated fatty acids other than arachidonic acid. This involves measuring enzymes in endometrial cells in tissue culture and observing the effects of polyunsaturated fatty acids on them.

Subfertility in dairy cattle

Prof APF Flint, Dr G Mann

If a dairy farmer put 100 cows to the bull 20 years ago, he would have expected to find 60 of them in calf after one mating. Today the figure would be 40. The same figures apply for artificial insemination, which is used throughout the dairy industry today. This drop in first service pregnancy rates of about 1 percent per year reflects several changes in dairy farming during this period - the drop in manpower available, changes in housing and nutrition, and a genetic correlation between milk yield and fertility. The genetic effect means that on average, selection of bulls with high producing daughters also results in selection for subfertility.

We have been seeking to halt the decline in dairy cow fertility through 3 approaches: by changing nutrition, by developing better treatments for infertility in individual cows, and by providing genetic information on which farmers can choose bulls with both good production and good fertility characteristics.

This work has led to the development and publication of the UK bull proofs for daughter fertility, which are now available to the industry through the Milk Development Council. It has also led to the development of molecular markers for fertility, in the form of single nucleotide polymorphisms which can be used to identify bulls with genotypes associated with improved daughter fertility. A further benefit has been the development of protocols for the improved veterinary treatment of repeat breeder cows.

Genetics of fertility have and the heritability of physiological reproductive traits

Prof J Wiseman

Studies on the genetics of fertility have led to a better understanding of the heritability of physiological reproductive traits.

Animal responses to nutrients

Prof J Wiseman

The emphasis on high lean tissue growth rate as a criterion for selection programmes in pigs has been highly successful. However there has been a concomitant increase in reproductive failure in females, particularly in the post-weaning gilt, although a causal relationship between the two has yet to be established. A programme to assess essential amino acid requirements of lactating sows, with a view to revising current data on recommendations of daily nutrient allowances for sows and gilts, is currently proceeding. A further programme in collaboration with the Meat and Livestock Commission is seeking to examine the influence of dietary inputs of the life-time performance of different pig genotypes, to include estimates of tissue accretion and the development of the reproductive tract. The influence of dietary inputs and patterns of tissue accretion in the gilt on puberty attainment and general reproductive performance are being studied through assessment of metabolic and endocrinological factors.

Neuroscience, Membrane Biophysics and Muscle Physiology

Opioid analgesia

Dr J Harris

Opioid administration is the principal pharmacological approach to treat acute pain in animals and humans (for example, morphine treatment following surgery). However against more chronic pain states, such as that due to tissue inflammation or nerve damage (neuropathic pain), the use of opioid drugs leads to inconsistent and unreliable results. Neuropathic pain in particular can be completely refractory to opioid treatment. An understanding of the mechanism of action of opioids, and why the effectiveness of these compounds is altered in chronic pain states, is therefore crucial for the development of improved analgesic therapies. It is well established that a principal site of action of the opioids is within the spinal cord where their inhibitory effect suppresses the transfer of noxious (painful) information from the periphery to the brain. Less is known about the mechanism of action of opioids in the brain, but it is thought they may disinhibit (i.e. activate) inhibitory nervous pathways descending from the brain to the spinal cord, thereby adding to the suppression of nociceptive information from the periphery. A change in the ability of the opioids to turn on these descending pathways may therefore underlie the altered efficacy of the opioids in chronic pain conditions. Our studies have therefore focused on identifying the descending pathways (noradrenergic, serotonergic) that are activated by brain-applied opioids (fentanyl, morphine), the receptors in the spinal cord that mediate the opioid-activated descending inhibition, and how these pathways interact with opioids applied at the spinal level. We have recently developed models of inflammatory and neuropathic pain to enable us to see if and how the interactions between opioids and descending pathways are altered in chronic pain states.

Primary sensory neurones and chronic pain

Dr S Kelly

Dr Kelly's work is currently focused on the role of primary sensory neurones in chronic pain conditions including arthritis. Primary sensory neurones detect and transmit somatosensory information to the central nervous system and as a result the sensations of touch, pressure, warmth, cool, or pain are perceived. In chronic pain conditions a population of primary sensory neurones that respond to potentially tissue damaging stimuli and signal pain (nociceptors), exhibit increased sensitivity to external stimuli, as well as spontaneous activity. These aberrant responses are thought to play an important role in the development and maintenance of chronic pain states. Spontaneous firing in nociceptors has been linked to spontaneous pain sensations, arguably the most distressing and poorly understood aspect of chronic pain conditions. It is vital that we understand the mechanisms leading to these changes, in order that we can develop useful analgesics for these often difficult to treat conditions. Targeting of the peripheral nervous system will hopefully lead to the development of drugs that have fewer side effects.

Dr Kelly is part of the research team that has recently established The Arthritis Research Campaign National Pain centre (www.nottingham.ac.uk/paincentre ). The Centre is funded by a substantial award from the Arthritis Research Campaign and has been created to investigate the mechanisms that lead to the chronic pain experienced by sufferers of arthritis, and to improve the treatment of that pain. Current work in Dr Kelly's group is also focused on the role of the peripheral cannabinoid receptor system in the modulation of inflammatory joint pain.

Organization of spinal reflexes

Dr J Harris and Dr A Waterfall

Withdrawal reflexes have evolved to help protect the body from potentially damaging stimuli by evoking rapid, automatic movement away from a potential source of threat. However in some musculoskeletal pain conditions, enhanced excitability of some reflexes (following inflammation or tissue damage) might lead to inappropriately prolonged activity that can lead to more pain. Our studies are therefore aimed at understanding the organization of reflex responses, and how exactly they are modified after injury, so we can start to think about new methods for treating these types of painful conditions. We have shown that relatively acute noxious stimuli (minutes in duration) can lead to quite prolonged changes in reflex responses (greater than an hour) which appear to be organized to enhance the protective function of the reflex: this means that a reflex can be inhibited, facilitated or remain unchanged depending on the movement produced by the reflex and the location to which the stimulus is applied. We have found that this organization is strictly controlled by the brain, therefore as long as descending pathways to the spinal cord are intact, only stimuli applied to the plantar surface of the foot (the load bearing structure) cause increased excitability of hind limb withdrawal reflexes:stimuli applied elsewhere either have no effect or cause reflex inhibition. However if the spinal cord is compromised, stimuli applied anywhere on the hind limb enhances reflexes in the limb and inhibition is very rarely seen. Of particular interest are the neurotransmitters that underlie these long lasting changes in reflex responses. Our research has shown that long lasting inhibition of reflexes is mediated by opioids and noradrenaline, whereas increased excitability in reflex pathways (a process known as central sensitization) is mediated by glutamate and the neurokinins. Since phenomena such as central sensitization are thought to be involved in the transition of pain from an acute to a chronic state, drugs that can block long lasting increases in excitability have enormous potential for the treatment of all types of persistent pain conditions.

Our current research in this area is now focused on measuring the actual reflex movements made in response to noxious stimuli, as all previous work on withdrawal reflexes has been based on the measurement of electrical signals: thus the movement is assumed rather than actually seen. Once the 'normal" organisation of reflex movements has been mapped, we can examine how reflexes are altered after disruption of endogenous control systems (see above) and by analgesic drugs. By combining motion analysis with electrophysiology we hope to provide a crucial link between behavioural and electrophysiological studies of pain, and by studying reflex movements in a model of inflammation, provide important data on the motor adaptations to arthritis.

Early life programming of brain function and behaviour

Dr C Stevenson

Early postnatal life is a crucial time for the maturation of the nervous system and insults during this critical period can result in seemingly permanent changes in brain function and behaviour later in life. For example, early adversity (e.g. abuse, neglect) increases the predisposition to develop various forms of mental illness (e.g. depression, anxiety, addiction) in adulthood. We and others model early neglect in the rat using maternal separation, where pups are separated from their mothers repeatedly during the neonatal period. As adults, rats subjected to early maternal separation show various behavioural and physiological disturbances such as enhanced fear and stress reactivity. They also show deficits in various learning and memory processes. We have recently demonstrated that these animals show abnormal activity in brain circuits involved in cognitive function and emotional regulation. These abnormalities may predispose the animals to be more vulnerable to the effects of stress. Interestingly, this research parallels brain imaging findings in humans which show structural and functional changes with early adversity. Ongoing work is examining the effects early maternal separation on fear learning and memory in adult rats to determine if this experimental approach provides a useful model of fear-related anxiety disorders, such as phobias and post-traumatic stress.

Dietary effects on animal production and product quality

Milk composition

Dr P Garnsworthy

I have conducted several large studies on nutritional and genetic factors influencing milk fatty acid composition. The primary aim is to improve the fatty acid profile of milk by reducing the propotion of saturated fatty acids and increasing proportions of monounsaturated and polyunsaturated fatty acids. Of particular interest is conjugated linoleic acids (CLA), which potentially have tremendous health benefits for humans. They are anticarcinogenic, anti-diabetic and anti-atherogenic; they alter nutrient partitioning away from body fat and improve the immune system. A major source of CLA is cow's milk. We have conducted several studies looking at seasonal variation in the CLA content of milk and mechanisms by which CLA is produced by cows in the rumen and mammary gland. We have shown that 80% of CLA is synthesised in the mammary gland via the desaturase enzyme system. In a study of 10,000 cows, we showed that desaturase activity has a heritability of 30%, so there are opportunities to breed cows for healthier milk.

Protected fat is widely used to increase dietary energy concentration for dairy cows. It is often observed that increasing dietary fat causes a depression in milk protein concentration. We have found that increasing the level of fermentable carbohydrates in the diet, in the form of lactose, can partially alleviate protein depression. Further studies have shown that rumen-protected protein can also help. The best results were obtained when protected fats were fed in combination with protected protein and lactose.

Nutritional control of factors affecting oocyte quality and improved dairy cow fertility.

Prof R Webb

An improved understanding of the nutritional control of factors affecting oocyte quality has led to feeding regimes now being implemented commercially to improve dairy cow fertility.

Nutritional evaluation of materials for inclusion into diets for non ruminant farm livestock

Prof J Wiseman

Cereals are the principal components of diets for non-ruminants. Current developments in this area include digestibility of starch and non-starch polysaccharides in cereals and digestibility of amino acids in new and isogenic wheat lines. The objectives of these two programmes are to examine possible variability in both biological and biochemical characteristics of cereals which might have been influenced by breeding programmes. Data generated have been extended into a DEFRA LINK programme with BBSRC John Innes Institute and SAC that is examining the environmental impact of poultry operations and how this might be reduced through selection of wheat cultivars of superior nutritional value. These studies are complemented by other research programmes which examine the influence of exogenous enzymes to enhance nutritional value of cereals, the influence of dietary components on gut environment and how these ingredients might influence gut morphology in poultry. A further programme (sponsored by DEFRA LINK with other UK Universities) in collaboration with the Division of Food Science is examining the digestibility of starch in the newly weaned piglet and the influence of processing of cereals. In vitro rheologoical analyses are employed to predict in vivo responses in meta-analyses. A recent DEFRA LINK programme is now extending these areas into poultry nutrition with a view to improving digestibility of wheat with an accompanying reduction in diffuse pollution from poultry operations.

These studies are now being extended to consider the nutritional value of plant legumes (as measured principally through amino acid digestibility determined in the small intestine) and quantification of the impact of anti-nutritional factors (primarily anti-trypsin factors) together with processing conditions designed to minimise their effects employing novel lines of peas developed at BBSRC John Innes Institute. Whilst studies are concentrated on young broilers, they are now being extended to the piglet. Dietary energy balance in growing pigs is being studied in a programme designed to estimate digestibility of components (carbohydrate fractions) both prior and post the terminal ileum, complemented with growth and serial slaughter trials whose ultimate objective is a more precise measurement of dietary energy availability. Within the major research programme `Finishing Systems Research' funded by MLC and DEFRA LINK, studies at Nottingham developed protocols for optimising energy / nutrient balance and minimising environmental load of liquid feeding systems in growing / finishing pigs. General nutritional evaluation of raw materials is an on-going programme.

Carcass quality

Prof J Wiseman

Qualitative aspects of both pig and poultry meat are assuming increasing importance. The growth of individual portions of the broiler carcass as influenced through dietary inputs has been studied in order to assess optimum conditions for growth and time of slaughter. Recent recommendations from Government bodies has identified the importance of essential fatty acid intake in the human population. Manipulation of the fatty acid profile of pig and poultry carcass fat through dietary means is well-known. However quantitative relationships between diet and carcass are less clear and are being studied. Areas of interest include the time for dietary changes to be mirrored in alterations in carcass fatty acid profile. Fatty acid profile of carcass fat may have a profound influence on eating quality. Thus an increase in the essential polyunsaturated fatty acid content of pig meat, whilst being perceived as being of possible benefit to the consumer, may also be associated with a decline in both keeping and eating quality because of the increased risk of oxidative degradation of these fatty acids producing off-odours and flavours. Previous studies involving taste panels have confirmed this. A study, in collaboration with colleagues in Food Science, attempted to quantify those compounds produced during oxidation of meat lipid through GC-mass spectroscopy.

Bioethics

Biofuels

Dr K Millar

The University of Nottingham is to lead the way in the development of sustainable bioenergy fuels — Ethanol and Butanol. These sustainable bioenergy fuels use non-food crops, such as willow, industrial and agricultural waste products and inedible parts of crops, such as straw, so do not take products out of the food chain. The CAB and the Institute for Science and Society will lead the social and ethical theme of two of six research projects being run by the University of Nottingham for the national £27m BBSRC Sustainable Bioenergy Centre. This is the biggest ever single UK public investment in bioenergy research.

Dog genomics

Dr K Millar

The EU project LUPA uses dogs to piece together the puzzle of human genetic disorders. The project, named after the she-wolf that according to Roman mythology cared for the twin founders of Rome is backed by EUR 12 million, involves scientists in 12 countries and will run until 2012. The CAB is employing the Ethical Matrix to encourage systematic consideration of the ethical issues raised for different stakeholders by the research.

Animal disease

Dr K Millar

The Network of Animal Disease Infectiology Research Facilities (NADIR) brings together 14 European laboratories holding level 3 biosafety clearance in order to, amongst other things, optimise their investigation and diagnostic/validation tools, achieve economies of scale and use the resources saved to modernise existing facilities in a coordinated manner. The CAB is contributing to the work package designed to strengthen the sharing of knowledge, best practice and consideration of ethical issues.