MICA - Developing novel single-cell multiplexing methods to identify drug targets for the treatment of multiple myeloma

Multiple Myeloma is a bone marrow cancer that affects over 5,700 new patients a year in the UK. Current response rates to treatment are varied and there is a mean survival age of only 4-5 years, with a 10-year survival rate of only ~3%. A significant proportion of treatment failure is due to the emergence of multi-drug resistance, which arise because of changes (mutations) in the nucleotides that form the building blocks of our DNA. RNA is a type of DNA and mostly acts as a messenger to carry out the instructions of DNA. Epigenetics is the addition of information on top of the DNA sequence that can modify the behaviour of a cell. This is achieved by adding a variety of chemical modifications or "marks" to the nucleotides.

Historically, scientists have investigated complex disease biology by mashing up pieces of tissue and taking biological measurements to work out the causes of disease. This is akin to blending fruit into a smoothie and then giving it to someone else to work out the ingredients by looking through the glass. Some fruit may be easy to identify, while others may be impossible to recognise. More recently, scientists have developed technologies that have allowed us to reconstruct the smoothie more easily by looking at its individual parts in finer detail. These "single-cell" technologies allow us to look at the components of the tissue one cell at a time and permit us to work out what may be causing disease. With this information we can design better drugs that target disease. In this fellowship, I will develop novel single-cell technology that are capable of capturing many more biological readouts than previously possible with currently technologies. This technology will then be applied to understand DNA, RNA and epigenetic mechanisms that contribute to the development of a bone cancer called Multiple Myeloma (MM).

In partnership with a biotechnology company, I have developed such a technology within in my lab that is capable of...