Dario Gerace

What qualifications do you hold?
Bachelor of Science (Honours) in Biomedical Science

Supervisors:
Professor Ann Simpson and Dr Rosetta Martiniello-Wilks

Research project title:
Gene and stem cell therapy for type 1 diabetes mellitus

Describe your research project
To some people, it comes as a surprise that there is more than one type of diabetes. Most people are familiar with Type 2 diabetes as it receives the most attention in the media. It is also represented by the large majority (85-90 per cent) of all people with diabetes. However, other types of diabetes also exist.

People with Type 1 diabetes (T1D) constitute about 10-15 per cent of people with diabetes, and the disease is characterised by high blood glucose levels. The reason being is that the immune system of people with T1D targets the insulin-producing cells (beta-cells) within the pancreas for destruction. When our immune systems target our own tissues/organs for destruction, it is otherwise known as autoimmunity. The function of insulin is to assist the tissues within our bodies to absorb glucose so that they can utilise it for energy production, however, since insulin is no longer produced in people with T1D, the glucose can no longer be absorbed by their cells and subsequently remains in the bloodstream resulting in high blood glucose. This can lead to complications such as loss of eye sight, loss of sensation in the hands and feet, and kidney damage.

To manage their blood glucose levels and maintain it within a normal range, people with T1D are reliant upon the lifelong use of insulin injections. However, insulin injections don't mimic the normal function of the beta cells, and as a result don't prevent the development of the aforementioned diabetic complications. Currently, the only cures are either pancreas or islet transplantation, however these treatments are limited by a shortage of organ donors.

As a result, I am trying to develop an alternative therapy as a cure for T1D. The concept is to replace the destroyed beta cells with "artificial" beta cells generated in the lab. Since stem cells have the capacity to turn into many different cell types, I target a specific type of adult stem cell known as a mesenchymal stem cells for conversion into "artificial" beta cells. Not only can mesenchymal stem cells be converted into different cell types, they also possess properties that allow them to evade destruction by the immune system! Therefore, by genetically modifying the cells so that they begin to express genes involved in the normal development of beta cells, I provide them with the genetic signals to turn into "artificial" beta cells and to begin producing insulin. In addition, these cells should also be able to evade the immune system!

However, before any therapies can be approved for human use, all preliminary research must be performed in animals to assess the safety and efficacy of the proposed therapy. As such, I use a diabetic mouse model to assess the success of the "artificial" beta cells that I create. The hope is that a transplantation of the "artificial" beta cells will cure people with T1D so that they no longer require insulin injections and do not develop life-threatening complications.

What is the aim of your project?
The specific aim of my research project is to generate "artificial" beta cells using a combinatorial gene and cell therapy approach for the treatment of T1D.

Why did you choose to pursue a research degree as opposed to going into the work force? Why this area of research?
I chose to pursue a research degree because it equips you with both a specific and highly transferable set of skills. Although you are technically defined as a specialist in your field, you possess the necessary skills to succeed in any area of work.

With regards to my area of research, I didn't exactly choose my project based on the disease I am investigating, but rather because I am interested in stem cell biology and tissue engineering through genetic manipulation.

What is your daily activity?
Being close to completion, most of my time is spent writing up the work I have completed to date in the form of a thesis. I still however do have experiments to perform, which involve designing and performing genetic cloning, maintaining stem cells in culture and monitoring animals. I am also a laboratory demonstrator for a number of undergraduate Science subjects.

What attracted you to research at UTS Science?
The modern facilities and the importance that the Faculty of Science has placed on raising the standard of research and output to a level comparable to the most well-known international universities.

What is your future?
I am fortunate to have confirmed my next career move in the form of a post-doctoral research position in the US. I will remain within the area of T1D research, in particular focusing on characterising the subset of immune cells involved in the development of T1D, and also utilising novel gene editing technologies to improve the efficiency with which "artificial" beta cells can be generated.