Dr Jose Polo encourages us to think of the human genome as a library. As an epigeneticist, expert in the way changes occur in our genes beyond the basic structure of DNA, Jose believes who we are is dependent on how the smallest, most fundamental pieces of our biology are able to open and close the great books of our genetic library.
The field of epigenetics is a complex one, rooted in the mechanisms and structures of gene expression deep within our body's cells. To the uninitiated this world can seem inaccessible, and so Jose has become accustomed to explaining just what his work entails, and how its real-world applications could shape the future of medical science.
At its most fundamental, Jose's work is driven by a desire to identify what really makes a cell a cell.
While different cells of the body have the potential to make different organs, the genomes, a catalogue of our hereditary information encoded as DNA are exactly the same.
'How is the cell of the skin different to the cell of the heart?" Jose says.
"The answer is not the genome, which is common throughout the body, but the genes that are expressed. There is no such thing as naked DNA, it is inside a nucleus and wrapped around neucleosomes and forming different complexes with proteins giving rise to the chromatin. This packaging determines the transcription or 'readibility' of the genes.
Through this concept of a gene's readability Jose's interpretation of the genome as a library takes shape.
'Both skin cells and heart cells have the same library - what is different are the books that can be read," Jose says.
"If each book is a gene, then whatever book is open is going to be transcribed. So if the keratinocyte (skin cells) books are open they get read and the cell become a keratinocyte,' Jose says.
Jose's work involves studying how these genetic books are opened and closed. He believes it is this process that makes us what we are - and what gives the cell its identity. And it this belief that offers a new direction for medical science.
Jose's desire to pursue this new line of thinking led him to leave his native Argentina for the US to do his PhD at Albert Einstein College of Medicine. Under the surpevision of Dr. Ari Melnick, he investigated how a family of transcription factors inhibit the reading of certain genes and led to the development of an anti-lymphoma agent. This is now going to clinical trials to be developed into a therapeutic.
He then was recruited to the group of Konrad Hochedlinger at Harvard University to work in the epigenetic and cellular mechanisms that govern reprogramming of adults cells into induced pluripotent stem (iPS) cells.
His worked attracted the interest of the Monash community in Australia and he is currently group leader in the Department of Anatomy and Developmental Biology. Further developing his genetic ideas into the realm of stem cell science, Jose is exploring the possibilities that will come out of the department's collaborative environment. He has already planned collaborations with researchers within the centre, as well as at the Australian Regenerative Medicine Institute, CSIRO, the University of Michigan and Cornell University.
The laboratory of reprogramming and epigenetics is led by Dr. Jose M. Polo who has recently relocated to Monash from Harvard University and has established his own research group.
The laboratory is interested in the transcriptional and epigenetic mechanisms that govern pluripotency and the reprogramming of somatic cells into induced pluripotent stem (iPS) cells.
Being able to specifically reprogram a mature cellular program into a pluripotent state and from there back into another particular cellular program provides a unique tool to dissect the molecular and cellular events that permit the conversion of one cell type to another. Moreover, iPS cells and the reprogramming technology are of great interest in the pharmaceutical and clinical settings, since the technology can be used to generate animal and cellular models for the study of various diseases as well as in the future, to provide tailor made cells for patients for use in cellular replacement therapies. However, despite being one of the major growing research fields very little is known about the epigenetic and transcriptome changes occurring during this process. We are particularly interested in three aspects:
Using different molecular, biochemical and cellular techniques our lab is aiming to dissect the nature and dynamics of such events.