Team:Newcastle/Choices

=Choices Rationale=

Why deal with cadmium?
The BacMan project is focused mainly on sequestering the heavy metal cadmium from contaminated soils, however with the many other heavy metals known to contaminate agricultural land, such as Mercury or Arsenic, it is necessary for us to justify our decision.

Cadmium Exposure
Cadmium is one of the most toxic heavy metals to which the environment can be exposed. Smoking is a major source of cadmium exposure to humans, however the main source of contamination to food is the usage of cadmium containing fertilisers and sewage sludge on agricultural land used for crops and vegetables (Jarup and Akesson. 2009).

The level of human exposure is dependent on factors such as dietary habits, and contamination of agricultural land. Exposure is significantly higher in China and Japan than in Europe and the US due to the high intake of rice grown on soil contaminated by local polluting industries (Nordberg et al. 2007). As well as food, water from rivers and wells can also be seriously contaminated. Cadmium is present in most foods however is particularly concentrated in molluscs, crabs and other shellfish, as well as tubular plants and root vegetables; cadmium is also concentrated in offal products such as kidney and liver.

As well as humans, cadmium exposure has implications for other species, with recent studies revealing cadmium exposure has serious effects on embryonic development of grazing animals (Nandi et al. 2009).

Cadmium can cause renal damage
In humans cadmium is nephrotoxic leading to damage to the proximal kidney tubules, which are the main site of accumulation.

Heavy metals such as cadmium have been shown to be involved in reactions that produce reactive oxygen species which leads to amplified lipid peroxidation, damage to DNA and an upset in calcium homeostasis (Manca et al., 1991; Kumar et al., 1996; El-Maraghy et al., 2001; Mendez-Armenta et al., 2003; Lopez et al., 2006).

There is evidence that cadmium serves as a competitive ion to calcium as it blocks all known calcium influx routes and also interferes with any neurotransmission initiated by calcium (Viarengo and Nicotera, 1991; Guan et al., 1988; Usai et al., 1999). However there is also evidence that cadmium ions increase the concentration of calcium in a cell – this concentration is usually cytotoxic leading to cell death (possibly the mechanism by which cadmium kills) (Orrenius and Nicotera, 1994).

Cadmium causes bone demineralisation
Exposure has also been linked to bone demineralisation. Cadmium was also responsible for causing a condition termed Itai-Itai Disease initially reported in a population in Toyama, Japan (Nordberg, 2004). The condition is characterised by the weakening of the bones, resulting in pain especially in the spine and leg bone areas. Progression of disease starts off as a gradually debilitating condition whereby the patient may find walking almost impossible. From that point onwards, the additional symptoms onset rapidly – these include kidney disorders, extreme pain, and bone breakage from the slightest of disturbances (an example is coughing). The end result is death (J.W. Hamilton, 2009).

Cadmium may cause cancer
It has also been recently suggested that low level exposure to cadmium can increase cancer risks, and cadmium has since been classified as a human carcinogen (Jarup and Akesson. 2009).

Cadmium is also a neurotoxic agent
Cadmium also has the ability to cross the blood-brain barrier, even though the amounts reaching the brain are small (Pal et al., 1993). The significance of the blood-brain barrier and cadmium neurotoxicity are confirmed in rat experiments, where infant rats suffer a larger degree of cadmium toxicity than do adult rats. The adult rats would have had more time for their blood-brain barriers to become established in comparison to newborn rats (Wong and Klaassen., 1982).

It has been reported that cadmium can provoke neuronal cells in the brain to undergo oxidative stress – the mechanism behind this is cadmium’s ability to encourage the production of reactive oxygen species when it interacts with the mitochondria (L´opez et al., 2006).

Cadmium can also affect the action of neurotransmitters. In studies, it has been shown to create an increase in concentration of inhibitory neurotransmitters (in particular GABA and Glycine) and create a decrease in the concentrations of excitatory neurotransmitters (in particular glutamate and aspartate) (Minami et al., 2001).

Why use Bacillus subtilis?
Bacillus subtilis strain 168 is the bacterial species of choice for the 2009 Newcastle team. It is a Gram-positive, catalase-positive bacterium commonly found in soil. We chose B. subtilis for its ability to live in a soil enviroments and for its ability to sporulate.

Some of our instructors and advisers know a great deal about B. subtilis and there is an active bacterial cell biology institute studying the molecular biology and physiology of this bacterium at Newcastle.

The 2008 iGEM Newcastle team and a number of other 2008 also used B. subtilis and provide a nice overview of its advantages in their wiki. Thanks to the efforts of these teams the number of B. subtilis parts in the registry is increasing. This year we have added many more.