Combining Microbiome Discoveries with Synthetic Biology Advances to Develop New Type 1 Diabetes Treatment

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Insulin delivery using infusion pumps can be effective for treatment of type 1 diabetes (T1D), but it does not completely protect T1D patients from the long-term effects of the disease or enable a normal, non-diabetic lifestyle. The solution JCVI is devising uses bacterial cells that naturally live in our body and have the capacity to function like our insulin cells, producing insulin when blood glucose levels are high to maintain proper glucose levels in T1D patients.

An important ingredient of this study is a set of bacteria recently discovered by our collaborator Richard Gallo at UC San Diego that naturally reside deep within the skin, in layers including the one used for administering insulin in current therapies. These bacteria do not cause problems in our body. Unlike transplants, they do not trigger host immune response. Unlike insulin pumps, they can enter this deep layer of the skin without puncturing the skin.

To make the deep-skin bacteria function like insulin cells, we will introduce a gene into them for making a version of insulin suitable for bacteria to make. We will also introduce a DNA piece containing three genes for making a glucose sensor to control insulin production in the bacteria. Importantly, we will delete a gene required for making thymidine, an ingredient for DNA, so that our bacteria will be able to grow only when we allow them to by providing thymidine within the laboratory. The critical test for this project will be to paint the body of a mouse with our bacteria and see if blood glucose levels drop.

Many rounds of experimentation and improvement will be needed in the future for establishing a system that can be tested in actual T1D patients. We expect that a positive result in our project will generate excitement in the field to fuel additional efforts toward a bacterial treatment of T1D that circumvents all the struggle of today's therapies.