Projects
1) Impact of
lysozyme milk consumption at the level of the intestine
Human milk
contains the antimicrobial compounds lysozyme and lactoferrin at
much higher levels than the milk of dairy animals. These
compounds are thought play a key role in the establishment of a
healthy gut microbiota in breast-fed infants. We are using milk
from transgenic goats expressing human lysozyme at levels 68% of
that of that found in human milk as a research tool to
investigate the consequences of bacterial changes in the gut on
overall health and the resistance to disease and as a potential
alternative medicine to combat intestinal infections. Work is
being carried out in pigs as a model for human health and
involves the profiling of intestinal bacteria and the
examination of gut histology and immune response.
2) Health and
well-being of transgenic animals
Transgenic
livestock of several species have been generated with the intent
to benefit animal agriculture. For instance, we have generated
transgenic dairy goats expressing the antimicrobial human
lysozyme in the mammary gland with the intent of improving udder
and animal health. It is hypothesized that the presence of an
antimicrobial in the milk of a dairy animal could lead to
decreased incidence and severity of mastitis. Mastitis, or
infection of the mammary gland, is not only detrimental to
animal well-being, but is also one of the most costly diseases
in the dairy industry. Work is underway to investigate the
antimicrobial nature of lysozyme milk by conducting in vitro
bacterial growth assays, milk shelf-life assays and mastitis
challenges.
In addition to
investigating the desired impact of the transgene in a
transgenic animal, transgenic animals must also be studied to
ensure that the presence of the transgene and transgene product
are not in any way detrimental to the transgenic animals
themselves. We have been investigating the reproduction, growth,
lactation and behavior of the lysozyme line of transgenic dairy
goats to generate information on the safety and well-being of
genetically engineered animals. Data along this line will be
useful to regulators and the general public in assessing the
safety of genetically engineered animals.
3) Enhancing
gene targeting in mammalian cells
The production
of transgenic animals is quite inefficient. Many techniques
employed result in the random integration of the transgene and
therefore, specific changes (such as knocking out a disease gene
or correcting a mutation) are difficult to achieve. In mammalian
cells, foreign DNA is preferentially integrated into the host
genome by the non-homologous end-joining pathway rather than the
desired route of homologous recombination. We are working
towards skewing the process more towards the homologous pathway
by transiently down-regulating key components of the
non-homologous end-joining pathway using siRNA. Tools are being
developed to accomplish this in both immortal and primary cell
cultures.
4)
Relationship between casein genotypes and milk production in
goats
The
as1-casein
genotype of a goat can have a profound impact on the amount of
milk a goat makes as well as the protein content of the milk.
This can have a large impact if the milk is to be used for
cheese-making. We have developed a genotyping scheme and are in
the process of typing a representative sample of the American
dairy goat population. Production records will be used to
correlate with genotype to determine if there would be an
advantage to selecting goats with certain genotypes. Selective
breeding can then be carried out to result in the desired milk
composition.
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