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Team:Humboldt Berlin

Fighting Cancer with Minicells

Salmonella Minicells for medical approaches in fighting cancer

TargetTaxi in Nuce

According to the RKI (Robert Koch-Institut, the biomedical lead research institution of the german government), an estimated half a million people develop cancer in Germany alone every year, and the trend is rising. This disease is also one of the leading causes of death worldwide. However, many therapy options are limited, which is why the development of new treatment approaches remains essential.

We aim to construct a synthetic system within the iGEM competition with the potential to become an alternative treatment method in the fight against cancer. To do so, we want to utilize minicells derived from Salmonella Typhimurium as a vehicle for anti-cancer protein agents. In addition, every component of the system will remain modular allowing researchers to utilize our tool easily. We wish for our system to be continuously adapted and improved based on new research findings, which means that the range of applications can grow as well.

Phase 1

Phase 1: Producing Minicells

We want to use Salmonella Typhimurium minicells as a shuttle or taxi system to fight cancer. We create the mini-cells by inducing asymmetric cell division in Salmonella bacteria, resulting in only small, nucleoid-free mini-cell creation. Minicells conserve most properties of the parental cells but are so small that they can only hold little amount of protein and plasmid. Strikingly, minicells lack the chromosome and relevant big machinery that bacteria need to grow and multiply, thus ruling out the risk of pathogenic infection in a clinical application. On the other hand, the small size is sufficient to guarantee the survival of the mini cell to reach cancer tissue. Additionally, minicells still can translate certain proteins and secrete them.

Phase 2

Phase 2: Cancer Cell Adhesion | Host cell specificity

Salmonella Typhimurium forms adhesins on its cell surface, which specifically bind to surface glycoproteins of the intestinal epithelium. These adhesins are important for the colonization and pathogenicity of the bacterium. We are therefore looking for tumor-specific glycoproteins and then create new antigens via mutagenesis so that our mini cells no longer adhere to cells of the intestinal epithelium, but instead specifically bind to cancer cells.

Phase 2

Phase 3: Protein Secretion

The virulence-associated type III secretion system (vT3SS) of S. Typhimurium is to be used for the secretion of proteins in order to invade the host cell.

This inject isome is a needle-shaped structure, anchored in the shell of the bacterial cell, through which proteins can be translocated into the host cell via the host cell membrane. Our mini cells also carry these injectisomes in sufficient quantities on their surface.

In addition, mini cells are metabolically active and can synthesize proteins from existing plasmids. Our goal is to construct a plasmid from which the minicells synthesize proteins, which are brought into the cancer cell via the needle-shaped secretion system. The cancerous cells are degraded by the toxic effect of the proteins. In this way, the tumor tissue could be eliminated in a targeted manner.

Financial Support

Cancer affects everyone in the long term. The disease is therefore not just a problem for a few, but a problem that we as a society have been reacting to for decades. With a variety of ways in research and development for more effective and more tolerable therapies. We want to do our part.

Cancer research is a very expensive branch of research. Regardless of whether this takes place in companies or public research institutes. For everyone involved, the question arises as to where the funds for this research should and should come from. Public research in particular wants to be accessible to the general public and usually has the claim to be independent in its research goals and methods. If possible, research funds are provided by the public purse so that this independence can be achieved in the best possible way.

As a student research group, we have extremely limited financial resources from the Federal Republic of Germany. In order to meet the demand for independence, we consider the financing of our research project as a cut across our society. In addition to donations from large companies in the healthcare and pharmaceuticals sector, we would also like to win small and medium-sized companies as partners who are active outside of our industry. We want to ensure that the diverse interests in our project are weighed against each other.

If you would also like to support us, we look forward to your inquiry and an open conversation.