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Science

The Francesca Gunn Laboratory



Senior Research Associate - Dr Evelyn Lewis 96-97

Dr Evelyn Lewis was interested in the hypothesis that ribozymes may be able to overcome the phenomenon called multi-drug resistance. This is a situation where cancer and leukaemia cells, having been exposed to chemotherapy agents once, can become to resistant (i.e not be susceptible) to the same and other chemotherapy agents.

She was able to demonstrate some effect of the ribozymes and presented some of this work at the British Association of Cancer Research Annual Meeting in 1997.* Lewis EL, Gibson I (1999) Modulation of P-glycoprotein expression inribozyme-transfected multidrug resistant (MDR) lung tumour cells.

Br. J.Cancer 81 (4): P15.Dr Helen James, a senior demonstrator, is working on a new project - involving the laboratory and the Norfolk and Norwich University Hospital - looking at how chemicals called calixarenes can be used to target leukaemia cells.

Helen James is analysing DNA samples at the Francesca Gunn Laboratory.

If that can be achieved, the drugs used against leukaemia will be more effective on the diseased cells, without affecting the rest of the body. The laboratory currently has 11 staff working within it, with two more expected to start this month.

"There are new people coming in all the time," said Prof Edwards. "A lot of what we do is short-term research contracts, and we are nationally and internationally recognised in terms of the work that we do in particular projects. " But an international reputation doesn't come cheap. And, although the Gunns' appeal has already raised a large amount of money, extra cash can always be utilised. A new drug to treat acute myloid leukaemia has been developed in Switzerland and Prof Edwards is hopeful that one day a similar breakthrough will happen nearer home. Currently, he and his team are tracking various genes in the body and finding out more about their association with cancer. Much of their research is done into breast and prostate cancer, which in turn will produce valuable information in the fight against childhood leukaemia. "We are trying to find out what makes some tumours more aggressive and others benign," he said.

Money from the Appeal helped buy this machine, the job of which is to extract leukaemia cells quickly.

"We have the technology to be able to look at tumours and what is going on with them, and are the leading laboratory in the world doing that. We collaborate with people all over the world. "Bryan Gunn's Leukaemia Appeal has provided some of the equipment at the laboratory. It is equipment like this, which could one day help the experts find a cure for leukaemia, that has made the appeal so worthwhile - and convinced Susan that fundraising was the correct step to take.



Phd Studentships Natalia Savelyeva PhD 1998

"Development and characterization of hammerhead ribozymes to target the RNA of the proto-oncogene c-myc"

Natalia was interested in the design and characterisation of a particular type of ribozyme called a hammerhead ribozyme. She created two ribozymes capable of cutting, and thus destroying, their target c-myc messenger RNA.

Her chosen target, c-myc, can be considered an oncogene. It can be amplified or modified in leukaemia (and cancer cells) so that it is inappropriately driving cell growth. An amplification of c-myc is seen inchronic myeloid leukaemia and a number of lymphomas for example. The hypothesis behind this work was the idea that if the c-myc levels were reduced back to normal by the ribozyme then the leukaemic cell may behave as normal as well.

Natalia used a type of cell called HL60 (which originally came from a patient with promyelocytic leukaemia) as her model system.

Phd Studentships Ciara Twomey PhD 1999

"Ribozyme delivery into the 32Db3a2 leukaemic cell line "One of the hurdles to be overcome if ribozymes are to be used astherapeutic agents is the lack of co-localisation within the cell ofribozyme and its target molecule.

Ciara was interested in where the ribozymes ended up within a cell (there being many different compartments within a cell) and whether the way in which they were introduced into the cell had an impact on their final destination.

Ciara used a different model system to Natalia. She used a cell line called 32Db3a2 which is a model forchronic myeloid leukaemia.



Brazilian Funding - Prof Dr Beny Spira, USP Brasil



University of East Anglia - Calixerene Project