Polo Lab research

Collaborations | Student research projects | Publications

About Professor José M. Polo

Professor José Polo, an ARC Future Fellow, 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, José 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 José 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, José'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?" José 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 nucleosomes and forming different complexes with proteins giving rise to the chromatin. This packaging determines the transcription or 'readability' of the genes.

Through this concept of a gene's readability José'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," José 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,' José says.

José'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.

José'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 supervision 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 and the Australian Regenerative Medicine Institute. Further developing his genetic ideas into the realm of stem cell science, José is exploring the possibilities that will come out of the department's collaborative environment.

Our research

Current projects and research themes

Prospective researchers please note: all of these projects contain a wet and a dry component, so biologists, biochemists, computational scientists, physicists and mathematicians are all welcome.

1. The kinetics and universality of the epigenetic and genomic changes occurring during reprogramming
2. The composition and assembly kinetics of transcriptional regulation complexes at pluripotency genes
3. How the cell of origin influences the in vitro and in vivo plasticity potential of cells generated during the reprogramming process
4. Induced human early embryogenesis
5. Neuronal maturation and neurodegeneration
6. Mechanism of transdifferentiation
7. In vitro disease modelling
8. Resolving cell heterogeneity by single cell “omics”

Visit Professor Polo’s Monash research profile to see a full listing of current projects.

Research activities

The Polo group is interested in the transcriptional and epigenetic mechanisms that govern cell identity and cell fate. It has a particular focus on pluripotency and the reprogramming of somatic cells into induced pluripotent stem (iPS) cells and other mature cell types.

Being able to reprogram any specific mature cell program into a pluripotent state and then back into any other particular cell gives the group a unique tool to study 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 pharmaceutical and clinical settings, as the technology can be used to generate animal and cellular models for the study of various diseases, as well as provide (in the future) specific patient tailor-made cells for their use in cellular replacement therapies.

^{Endothelial cells obtained from keratinocytes cells by transdifferentiation according to Mogrify predictions produced in the Polo lab .
Image created by Jaber Firas. Courtesy of Nature Genetics & Rackham and Firas et al. 2016.}

^{How to make pluripotent cells: playing with the molecular make-up. (Image designed and provided courtesy Scot Nicholls scot@ancientlakes.com.au)}

The Polo group is dissecting the nature and dynamics of different processes where cell fate is dynamic (reprogramming, differentiation, pluripotency, disease, neurogenesis, ageing, transdifferentiation) using a broad array of approaches through the use of mouse models and a combination of different molecular, biochemical and cellular techniques, and genome-wide studies.

• Human naïve pluripotent stem cells, iPSCs, reprogramming
• Cell signalling, in vitro differentiation, neural differentiation, pluripotent stem cells, cardiac
• DNA methylation, Oct4, Sox2, chromatin remodelling, refractory cells, reprogramming intermediates, transcriptional    waves
• Mogrify, cell conversion, FANTOM5 data set, transcription factors
• Human Development, Stem Cells & Regeneration, Genetics, Bioinformatics
• Neuroscience: Neurodegenerative Diseases, Neural Mechanisms in Diseases and Disorders, Understanding the Brain, Bioinformatics
• Immunology: Innate immunity, adaptive immunity, Inflammation

^{Professor José Polo and Dr Anja Knaupp, a research fellow in the Polo lab, explain their research, using stem cells to advance our understanding of how the body develops and what happens during disease. Video courtesy of Stem Cells Australia}

^{Bioinformatic figures                                                                          Teratoma for press release}

In 2006, the Japanese researchers who made the Nobel Prize-winning discovery of induced Pluripotent Stem (iPS) cells identified a set of four transcription factors as being capable of turning any cell into iPS cells. These iPS cells, as with embryonic stem cells, have the potential to produce any cell of the body, but avoiding the use of embryos or carrying the risk of being rejected by the patient’s body, a limitation of transplantation. Yet a decade later, it was still not fully understood precisely how these reprogramming factors work – until a suite of papers published in Cell Reports, Cell Stem Cell, and Nature Methods in 2017 shed light on vital aspects of cell reprogramming.

Mogrify
In what is likely to revolutionise the ability of doctors to turn cells from a patient into tissues and organs needed to treat disease, a technology called Mogrify, co-developed at Monash University, provides the template to turn cells into a heart, kidney or pancreas. Monash researchers, in collaboration with colleagues at the University of Bristol, UK,and Riken in Japan, published a landmark Nature Genetics paper in 2016 which outlined a program, called Mogrify, that effectively provides researchers with the “recipe” for turning human cells into any desired cell from a tissue and organs such as blood vessels and cardiac tissue. Since the publication, the researchers at Monash University and the University of Bristol have created a spin-off biotech company, Cell Mogrify. Funding from a UK angel investment group will allow Cell Mogrify to provide and test the blueprints for turning cells into specific cells, highly needed in the pharmaceutical industry. This will be used in drug and toxicity testing as well as clinical settings.

“Mogrify turns what had previously been a ‘hit and miss’ approach to creating specific cells from tissue and organs in the lab, to a fast, accurate system for generating cells for the clinic and pharmaceutical industry,” lead researcher, Monash BDI’s Professor José Polo said

Cell Therapy company recognised at prestigious business awards, April 2019

Monash researchers start company to reprogram human cells, November 2016

^{This image is a graphical rendering of a map of the transcriptional signature of human cell types taken from Rackham and Firas et al. 2016 Nature Genetics (supplementary figure 2). Human cell types are positions on the surface; the coordinates are derived from expression profiles in combination with reprogramming potential between types as generated by Mogrify (http://mogrify.net). Image created by Cherrie Kong.}

Techniques/expertise

We use mouse models and a combination of different molecular, biochemical, cellular techniques and genome wide approaches (RNA-seq, MS-MS, ATAC-seq, ChIP-seq, SC-RNA-seq, etc)  to dissect the nature and dynamics of such events.

Disease models

• Rubinstein-Taybi Syndrome
• Alzheimer’s Disease
• Ageing
• Prostate Cancer
• Inflammation

Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Student research projects

The Polo Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.